"I have realized a while ago that the nature of politics don't suit my professional background as a judge," his resignation letter, read on state TV, said. He said he had first submitted his resignation last month but events forced him to stay on.
The resignation underlines the costs Morsi is paying in the bruising constitutional fight, the country's worst turmoil since the fall of autocrat Hosni Mubarak nearly two years ago. Morsi will likely win the victory of the charter's passage. But he has been abandoned by many of the figures he brought into his administration to give it a more broad-based image, leaving him even more reliant on the Brotherhood and ultraconservative Salafis.
Over the past month, seven of Morsi's 17 top advisers and the one Christian among his top four aides resigned. Like Mekki, they said they had never been consulted in advance on any of the president's moves, including Nov. 22 decrees placing him above any oversight and granting himself near absolute powers.
Saturday's vote is taking place in 17 of Egypt's 27 provinces with about 25 million eligible voters. The first phase on Dec. 15 produced a "yes" majority of about 56 percent with a turnout of some 32 percent, according to preliminary results.
Preliminary results for the second round are expected late Saturday or early Sunday. The charter is expected to pass, but a low turnout or relatively low "yes" vote could undermine perceptions of its legitimacy.
For some, the vote was effectively a referendum on Morsi himself, who opponents accuse of turning the government into a monopoly for the Muslim Brotherhood.
In the village of Ikhsas in the Giza countryside south of Cairo, buses ferried women voters to the polling centers in an effort villagers said was by the Muslim Brotherhood.
An elderly man who voted "no" screamed in the polling station that the charter is "a Brotherhood constitution."
"We want a constitution in the interest of Egypt. We want a constitution that serves everyone, not just the Brotherhood. They can't keep fooling the people," 68-year-old Ali Hassan, wearing traditional robes, said.
But the draw of stability that many hope will come from having a constitution was strong. Though few fault-lines in Egypt are black and white, there appeared to be an economic split in voting, with many of the middle and upper classes rejecting the charter and the poor voting "yes."
In Ikhsas, Hassan Kamel, a 49-year-old day worker, said "We the poor will pay the price" of a no vote.
He dismissed the opposition leadership as elite and out of touch. "Show me an office for any of those parties that say no here in Ikhsas or south of Cairo. They are not connecting with people."
As was the case in last week's vote, opposition and rights activists reported numerous irregularities: polling stations opening later than scheduled, Islamists outside stations trying to influence voters to say "yes," and independent monitors denied access.
For the past four weeks, both the opposition and the Islamists have brought giant crowds out into the streets in rallies first over Morsi's grab of new powers, though they were since revoked, and then over the charter itself, which was finalized by a Constituent Assembly made up almost entirely of Islamists amid a boycott by liberal and Christian members.
The rallies and protests repeatedly turned in to clashes, killing at least 10 people and wounding more than 1,000. The most recent came on the eve of Saturday's voting, when Islamists and Morsi opponents battled each other for hours with stones in the Mediterranean city of Alexandria.
The promise of stability even drew one Christian woman in Fayoum, south of Cairo, to vote "yes" a break with most Christians nationwide who oppose the draft. Hanaa Zaki said she wanted an end to Egypt's deepening economic woes.
"I have a son who didn't get paid for the past six months. We have been in this crisis for so long and we are fed up," said Zaki, waiting in line along with bearded Muslim men and Muslim women wearing headscarves in Fayoum, a province that is home to both a large Christian community and a strong Islamist movement.
In the neighboring village of Sheikh Fadl, a car fitted with loudspeakers toured the area with a man shouting, "Yes, yes to the constitution!" In the city of Fayoum, a man could be seen painting over posters urging people to vote "no."
In Giza's upscale Mohandiseen neighborhood, a group of 12 women speaking to each other in a mix of French, Arabic and English said they all intended to vote "no."
"My friends are Muslim and are voting 'no.' It's not about Christian versus Muslim, but it is Muslim Brotherhood versus everyone else," said one of them, Shahira Sadeq, a Christian physician.
Kamla el-Tantawi, 65, voted with her daughter and grand-daughter. "I voted 'no' against what I'm seeing," she said, gesturing to a woman standing close by wearing the full-face veil known as niqab, a hallmark of ultraconservative Muslim women.
"I lose sleep thinking about my grandchildren and their future. They never saw the beautiful Egypt we did," she said, harkening back to a time decades ago when few women even wore headscarves covering their hair, much less the black niqab that blankets the entire body and leaves only the eyes visible.
In the neighboring, poorer district of Imbaba, Zeinab Khalil a mother of three who wears the niqab was backing the charter.
"Morsi, God willing, will be better than those who came before him," she said. "A 'yes' vote moves the country forward. We want things to calm down, more jobs and better education."
The voices reflected the multiple concerns that have been shaking Egypt for weeks. For some, the dispute has been about Shariah and greater religion in public life whether to bring it about or block it. In many areas, clerics have been preaching in favor of the charter in their sermon.
But the dispute has also been about political power.
An opposition made up of liberals, leftists, secular Egyptians and a swath of the public angered over Morsi's 5-month-old rule fear that Islamists are creating a new Mubarak-style autocracy.
Morsi's allies say the opposition is trying to use the streets to overturn their victories at the ballot box over the past two years. They also accuse the opposition of carrying out a conspiracy by former members of Mubarak's regime to regain power.
Many voters were under no illusions the turmoil would end.
"I don't trust the Brotherhood anymore and I don't trust the opposition either. We are forgotten, the most miserable and the first to suffer," said Azouz Ayesh, sitting with his neighbors as their cattle grazed in a nearby field in the Fayoum countryside.
He said a yes would bring stability and a no would mean no stability. But, he added, "I will vote against this constitution."
In Ikhsas village, Marianna Abdel-Messieh, a Christian, was the only woman not wearing a head scarf in the women's line outside a polling center. She was voting "no," but expected that whatever the result, Egypt would see more rule by Shariah.
"So, whether this constitution passes or not, there will be trouble," she said. "God have mercy on us."
Michael reported from Fayoum. Associated Press writer Sarah El Deeb contributed to this report from Giza.