In San Francisco, Caltrans crews will close two lanes in both directions of Highway 101 near Hospital Curve from 11 p.m. Friday through Monday morning.
The lane reductions are part of a road improvement project aimed at reducing flooding in the corridor ahead of the upcoming winter storm season.
"This is really needed because if you remember when there's big storms, the area floods a lot," said Caltrans spokesperson Pedro Quintana. "New drains will help crews fix the issue and be ready for next storm season."
The closure will impact about a one-mile stretch of the Bayshore Freeway near Zuckerberg San Francisco General Hospital.
Residents who live near the freeway say the area is already known for congestion.
"What I can tell is it's gridlock all weekend long," said Potrero Hill resident Karen Schneider.
Schneider says she's personally experienced lengthy backups around Hospital Curve.
"I've definitely been stuck in two to three hours of traffic trying to get to and from Oakland on a weekend for a catering job," she said.
For workers who regularly commute into the city, the construction means adjusting travel plans. "For most people coming to the city, it's going to be frustrating," said Isabella Japec, who works weekends at Deli 23 near San Francisco General Hospital and commutes from the East Bay.
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Her solution: leave earlier. "Half an hour early," Japec said when asked about her plans for Saturday.
Caltrans is encouraging drivers headed into San Francisco to consider alternate routes, including Interstate 280 and Highway 1.
Meanwhile, another major traffic impact is expected in the North Bay, where the westbound Carquinez Bridge will be fully closed for 53 hours beginning Friday night and continuing through early Monday morning.
The closure is part of a bridge deck replacement project.
"If you're heading down from Sacramento toward San Francisco, there will be no access past the 780 freeway," said Caltrans spokesperson Bart Ney.
Drivers traveling to communities such as Crockett, Rodeo and Hercules will be directed to use Highway 4 as part of the detour route.
Caltrans advises motorists to follow posted detours and expect delays on Interstate 780, Interstate 680 and the Benicia Bridge throughout the weekend.
Officials urge travelers to plan ahead, allow extra time for their trips and consider alternate routes whenever possible.