Owen Farrell's comeback from repeated ankle injuries has stalled for concussion reasons arising from Saracens' Gallagher Premiership victory over Bristol.
Farrell was replaced in the 71st minute of the clash in north London on Saturday after departing for an HIA, which he passed.
However, the England playmaker has still been following the return-to-play protocols this week and has not been picked for Friday's visit to Sale.
It is another blow to the 30-year-old, who was making his comeback after four months out because of injuries to each ankle, the first of which was sustained during England's autumn campaign.
He was poised to return for Saracens in January, in the process aiming to prove his fitness in time for the Six Nations, only to damage the same joint on his other leg during training.
Farrell's 12-point haul was key to securing a 27-23 victory over Bristol at Tottenham Hotspur Stadium, although he also produced the type of controversial tackle that has littered his career.
The veteran of three Lions tours can ill-afford any more setbacks as he battles to reclaim a place in England's midfield, as well as the captaincy role that has been filled by Courtney Lawes and Tom Curry in his absence.
Sale boss Alex Sanderson, who coached Farrell when at Saracens, believes he will be a big loss for Friday's clash.
"Owen's ability to wrestle back momentum because of the respect and his ability to communicate what is needed, is second to none. What he does on the field, and in and around it, brings everyone else up," Sanderson said.
Tuilagi makes return for Sale
Manu Tuilagi will make his latest comeback from injury as a replacement in Friday's game when Sale host Saracens at the AJ Bell Stadium.
Tuilagi was picked at inside centre to face Wales in round three of England's Guinness Six Nations on February 26 only to be withdrawn hours later because of a hamstring injury.
It was set to be his first international appearance since the autumn when he damaged the same hamstring while scoring a try against South Africa and he has not played since.
Eddie Jones called the powerful centre into their Six Nations squad after he completed just 81 minutes of rugby for Sale, whose director of rugby Sanderson believes he was rushed back too soon.
It was the demands of England training that caused the latest setback in a career beset by injury but the Sharks hope he will now stay fit as they look to reach the latter stages of the Premiership and Heineken Champions Cup.
Tuilagi's destructive carrying in midfield has been missed by club and country with Jones to date unable to find an alternative capable of getting the team on to the front foot through force.