Siemian was tabbed to start coach Gary Kubiak after Thursday's joint practice session with the 49ers.
Mark Sanchez, who started the preseason opener, will be the No. 2 signal caller against San Francisco.
"They should both play with the [first team] somehow, some way this week," Kubiak said. "We'll see how the reps fan out."
Siemian, 24, was a seventh-round pick out of Northwestern in the 2015 NFL draft and has never thrown a pass in a regular-season contest. He went 7-of-12 for 88 yards in the preseason opener against the Chicago Bears.
Sanchez has played seven NFL season with the New York Jets (2009-13) and Eagles (2014-15) and has thrown 86 career touchdown passes and 84 interceptions. He was 10-of-13 for 99 yards with one touchdown and one interception against the Bears.
Kubiak estimated that both Siemian and Sanchez will play about 1 1/2 quarters on Saturday. First-round pick Paxton Lynch will play the remainder of the contest.