The closure is necessary because of ongoing construction on a pedestrian bridge over Fannin at Texas Children's Hospital.
Metro says the interruption in service starts tomorrow night and continues through midnight Sunday. The transit agency's Carolina Mendoza says buses will still be available along the route.
"The buses will stop, we call it Route 700, and there are signs along the rail line, so they're located in close proximity to where the rail stations are. So those who normally would board at the downtown transit center, they'll see along Main Street one of the bus location stops right there. And we'll also have personnel out there assisting patrons."
Mendoza says light rail service will also be stopped twice next month.
Both of those interruptions all also on weekends when the Houston Texans are on the road. Many Texans fans use light rail service on game days. The Texans are set to play in New Orleans this weekend.