Ben Revere, originally slated to play left field, made the start in center field in his place, as Trevor Plouffe moved from second base to left field and Matt Tolbert started at second.
Span, who missed 48 games with his concussion before returning on Aug. 2, has struggled since making his return, batting just .057 with nine strikeouts and three walks in 38 plate appearances.
He asked for the day off in Cleveland on Sunday -- in a game that was eventually rained out -- and was expected to play on Monday, as he was originally penciled in as the club's center fielder and leadoff hitter.
Twins manager Ron Gardenhire hinted before the game that Span could be removed from the lineup if he dealt with any concussion symptoms.
"If he has any issues I'll take him out, and make adjustments from there," Gardenhire said before the lineup change was announced.