Con Edison, the city's main power company, said there are at least 123,808 customers without power, including those who had previously lost power as a result of the storm, as of 6:30 a.m. Friday.
The new power outages in New York City Friday, according to Con Ed's outage map, were in the Upper West Side, Harlem and Upper East Side neighborhoods.
ConEd, in a statement to ABC News, said the supply has been restored to those areas.
"We are investigating a problem on our transmission system that caused three networks in Manhattan to lose their electric supply at about 5:13 this morning," ConEd said in a statement.
A live camera from ABC News New York City station WABC showed a large section of the Upper West Side completely dark. A station camera also showed the electricity out in the Upper East Side.
Subways in the city are also being impacted because of the Manhattan power outage, according to the Metropolitan Transit Authority.
Lines impacted, according to the MTA, including the A, B, C, D, 1,2,3, E, F, N, Q, and R trains.
"Expect delays as we are getting reports of power outages in some parts of uptown Manhattan," the MTA tweeted. "This is also affecting stations and third-rail power."
Thousands have been without power in the city this week as a result of Isaias.
"We realize it is incredibly frustrating to be without power and that is why we are working around the clock to get customers back in service," Robert Schimmenti, Con Edison's senior vice president, Electric Operations, said in a statement Thursday. "We have additional mutual aid and contractor workers arriving each day to help us restore service safely. We assure our customers that our crews will remain on the job 24-7 until everyone has their power back."
ABC News' Aaron Katersky contributed to this report.