Simmonds was replaced at half-time of Saturday's 12-6 victory over Wales at Twickenham because of a shoulder injury and has returned to his club Exeter for treatment.
The number eight has been omitted from the 32 players picked by Eddie Jones and Press Association Sport understands he is likely to miss the trip to Murrayfield on Saturday week.
READ MORE: Townsend thrilled with Scotland improvement
READ MORE: Jones pleased to beat ‘very cocky’ Wales
He was a star performer in the round one rout of Italy in Rome, running in two tries to sound his arrival as a genuine option for England at number eight.
His absence would be mitigated by the possible availability of Nathan Hughes, however, after the Wasp made a successful comeback from a knee injury on Sunday.
Further cover in the position is provided by Sale's Cardiff-born England Under-20 star Sam Moore, who is present as an 'apprentice player' and had previously been on Wales' radar.
Joe Marler's availability following completion of his six-week suspension for dangerous clearing out of a ruck means rookie prop Alec Hepburn has been sent back to Exeter.
Second row George Kruis has been dropped following Charlie Ewels' recovery from a hamstring injury and James Haskell is also available to face Scotland after serving a four-week ban for a dangerous tackle.
Harlequins wing Gabriel Ibitoye makes his first appearance in a senior England squad following his inclusion as an apprentice player.
Ibitoye scored a stunning try for the under-20s against Wales last Friday and has been rewarded with a place in the training squad.
England's pack will scrummage against Georgia on Tuesday and Wednesday after it was arranged for the Eastern Europeans to fly over for the training sessions in the Six Nations' first fallow week.