Elliot Daly and Jamie George have pulled out of the England training squad that is preparing for the Six Nations opener against Scotland.
Centre Daly suffered a hamstring injury and hooker George was concussed in Saracens’ loss to Edinburgh on Sunday.
George could return to Pennyhill Park later this week if he progresses through return-to-play protocols.
Newcastle hooker Jamie Blamire and Bath centre Ollie Lawrence have been called up as replacements.
New England head coach Steve Borthwick has already had to deal with a number of injuries as he prepares for his first match in charge against Scotland at Twickenham on 4 February.
Key forward Courtney Lawes and hooker George McGuigan pulled out of the squad on Monday with calf and knee injuries respectively, while Exeter number two Luke Cowan-Dickie will miss at least the start of the tournament with an ankle problem.
Northampton lock David Ribbans and Bath hooker Tom Dunn were added to the squad on Monday for the five-day training camp.
After their tournament opener against Scotland, England host Italy on 12 February.
A trip to Wales follows on 25 February before a home game against defending champions France on 11 March precedes their final game against Ireland on 18 March in Dublin.