George Ford is the latest England star to face a Six Nations fitness race.
The fly-half is missing Sale's Champions Cup trip to Cape Town this week, to have injections to help heal a kneeligament problem.
Any absence at the start of the Six Nations for Ford would leave the path clear for Harlequins star Marcus Smith to receive the keys to England’s backline.
England will be without talismanic fly-half Owen Farrell for the Six Nations, after the 32-year-old opted for a break from Test match rugby.
Northampton’s in-form Fin Smith is bound to command selection to head coach Steve Borthwick’s wider Six Nations squad, but Ford remains one of England's top lieutenants.
Ford will number among the genuine captain contenders in Farell’s absence, though Jamie George and Ellis Genge are the frontrunners.
So Borthwick will want Ford back in action as soon as possible, with England opening their Six Nations campaign against Italy in Rome on February 3.
Sale will face the Stormers in South Africa on Saturday, but Ford will not be on hand for the Sharks.
“George didn’t travel because he needs injections in his leg, in his MCL, to stiffen it up,” said Sale rugby director Alex Sanderson.
“I would have loved him to be here but he just wants to do what is best for his knee, for us and for England, if selected. So he had two injections this week.”
England will already be without injured prop Bevan Rodd for the entire Six Nations due to a foot problem, while Sale flanker Tom Curry will miss the rest of the season after hip surgery.
Bristol prop Genge is a doubt for the start of the competition due to hamstring trouble, while Harlequins front-rower Joe Marlerremains in the dark about the extent of his biceps injury.