Harden turned the ankle late in Thursday's win over the Kings, but he was not listed on the official injury report. The Rockets announced that he would not play about 30 minutes before the game, after Harden had gone through his pregame shooting routine.
Rockets coach Stephen Silas said he first heard a few hours before tipoff that Harden's ankle was bothering him enough that it might cause him to sit out the game.
"He was just going to see how it felt, and obviously it didn't feel good enough for him to play," Silas said after Houston's victory. "For us to win this game without him is pretty special."
Harden, the NBA's scoring champion the past three seasons, is averaging a league-leading 37.0 points and 11.0 assists through three games.
Eric Gordon, one of three key Rockets players who missed the season-opening road trip because of the league's health and safety protocols, replaced Harden in the starting lineup.
Gordon had 21 points and four assists in the Rockets' win on Saturday.