Blythe limped off after just four minutes of the 36-16 Betfred Super League defeat at the Mend-A-Hose Jungle and he could miss a significant chunk of the remainder of the season.
His absence is at least offset for Saturday's Ladbrokes Challenge Cup quarter-final against Wigan Warriors by the return of Ryan Atkins after a hernia issue.
Coach Tony Smith said: "Matty Blythe has picked up an innocuous-looking injury but has ended up with a fracture in the bones in his lower leg. That makes it more long term than we at first suspected."
Injury news: Blythe out small fracture to lower leg. Gids, Atkins & Brown a chance this wk to have fitness tests. Wilde also in contention
— Warrington Wolves (@wolvesrl) June 14, 2017
Creative players Kurt Gidley and Kevin Brown will face fitness tests after calf and foot injuries respectively but Matty Russell is still out with a knee problem.
Prop Chris Hill is missing through suspension after being handed a one-match ban for reckless striking with the shoulder against the Tigers.
Smith, whose side have lost their last four games, said: "We could have some experienced heads returning in important positions, so we're focusing on what we have returning rather than what we haven't."
