Milner limped off with a hamstring injury soon after scoring City's second goal in their 2-0 midweek win at Wigan. The 26-year-old could also be doubtful for next week's Champions League trip to Borussia Dortmund and the derby with Manchester United which follows, but City are not yet sure of the seriousness of the problem.
Manager Roberto Mancini said: "James is out for tomorrow (Saturday). We will try to recover him for next Sunday but we don't know."
Milner had been making only his second appearance since returning from a lay-off with a similar injury.
He came on as a substitute just before the hour at the DW Stadium, scored with a superb long-range strike after 72 minutes and then hobbled off to obvious frustration nine minutes from time.
When asked about the player's disappointment, Mancini said: "It is normal. He played against Chelsea and played very well. He came back after injury, now he played 20 minutes and had a hamstring (injury). We are disappointed because James was in good form in this moment."