England forward Poppy Cleall and centre Amber Reed will be unavailable for Sunday's Women's Six Nations match against Italy after sustaining knee injuries against Scotland.
The Rugby Football Union said Cleall and Reed "are targeting a return for the latter rounds" of the tournament.
England's centre options were already reduced, with Emily Scarratt injured.
In Scarratt's absence, Reed initially took on goal-kicking duties on Saturday and Lagi Tuima took over when the inside centre was injured.
Tuima and Tatyana Heard, who usually play 13, are the existing choices for the Italy fixture in Northampton.
Uncapped Exeter centre Nancy McGillivray was pulled off early while playing for England Under-20s on Saturday, suggesting the 20-year-old could be included this weekend.
England seek a fifth successive Six Nations title and their final-round match against France at Twickenham on 29 April will likely be the tournament decider.