Shane Illingworth made his third career start at quarterback in place of Sanders, who has missed at least a portion of seven games in the past three seasons. Illingworth threw for 315 yards on 22-of-40 passing and raced Oklahoma State down the field on its first offensive possession, connecting in the end zone with Tay Martin.
Sanders missed two games early last season because of an ankle injury. He missed most of the final three games of his redshirt freshman season in 2019 with a hand injury. He was named the Big 12 Freshman of the Year that season.
Sanders, a redshirt junior, passed for 2,007 yards and 14 touchdowns with eight interceptions in 10 games last season.
Illingworth played in four games last season as a true freshman and started against West Virginia and Kansas.
The Cowboy Radio Network first reported that Sanders would miss Saturday's opener due to COVID-19 protocols.
The Associated Press contributed to this report.