The mayor released a statement saying she is leaving her role to focus her attention on the family.
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"Serving the people and the city I love dearly as Mayor has been an honor. My love for Durham and its citizens has never wavered, and it never will. However, at this time in my life, my attention has shifted to prioritizing my family. Therefore, I will not seek another term."
O'Neal took office in 2021 replacing former Durham Mayor Steve Schewel.
ABC11 spoke with Mayor Pro Tem Mark-Anthony Middleton and others to understand why O'Neal decided not to run for re-election.
Nate Baker is on the Durham Planning Commission -- and is running for council -- and said he believes recent turmoil on city council may have been a factor.
"There's little doubt right now that that the political dynamics on council are extremely challenging," said Baker. "And I think that just took its toll on her. I think that she decided that there were things that she could do outside of being mayor, outside of council that were better worth her time."
The Mayor's announcement came amid an active extortion investigation into councilor Monique Holsey-Hyman, and a politically fractured city council. But Middleton said this decision isn't about that.
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"She's got a lot of experience and a lot of service under her belt," he said. "I'm not going to begrudge her or second guess one bit. If she says she wants to be with family, she's earned it. And we should just take it at face value."
The announcement also came less than 30 days from the filing deadline to run for mayor, which Baker said may create some waves for potential candidates.
"You know, there are a few names that have been floating around out there. We're going to see some surprises. There's going to be a scramble for who is going to become the next mayor of Durham," Baker said.
As far as a successor goes, Middleton said Durham residents want someone they can trust, and who treats the office and fellow council members with respect.
"I think the folk in this city deserve and want and desire non-toxicity in city hall. I think they want a city council that when we're not in session are brand ambassadors for the city, whether we're in session or not in session, and the council that can work together," Middleton said.