The young forward appeared to roll his ankle less than 20 minutes into the game, having already provided the assist for Gabriel Martinelli's opening goal.
Saka was also on the wrong end of a few tough tackles from Forest's Renan Lodi, and was soon limping and grimacing.
Club doctor Gary O'Driscoll assessed Saka on the pitch and soon let the player try to run it off, but after a miscued attempt at goal on the volley, he called it a day.
It remains to be seen how serious Saka’s injury is. Mikel Arteta will address the media following the game.
Gareth Southgate is due to announce his England squad for the World Cup in 11 days’ time, with the Three Lions’ first match in just over three weeks’ time.