Leicester Tigers winger Jonny May faces an “extended period” out after fracturing a cheekbone in England’s Six Nations win over Wales on Saturday.
The 29-year-old was forced off at Twickenham and has had surgery.
Back row Sione Kalamafoni, 31, and fly-half Johnny McPhillips, 22, will also be long-term absentees through injury.
Kalamafoni will miss three months after suffering concussion symptoms, while McPhillips is out for a similar time with a ligament tear in his right knee.
“As we enter the final half of the Premiership season and approach the knockout stages of Europe, the loss of three players is a blow,” said Leicester head coach Geordan Murphy.
“We are fortunate to have returning players from the Six Nations to add vital depth to the squad.”
Tonga international Kalamafoni has been stood down by a neurologist after Leicester’s weekend defeat by Saracens. McPhillips was also forced off in that game, his first Premiership start for the club.