Newcastle forward Michael Owen has been ruled out for up to six weeks with ankle ligament damage.
The 29-year-old England striker limped off 19 minutes into the 2-1 defeat by Manchester City at St James' Park.
It comes two days after midfielder Joey Barton, 26, was sidelined for up to 10 weeks after breaking the fifth metatarsal in his right foot.
Reacting to losing Owen, Newcastle boss Joe Kinnear said: "It's a big blow and the injuries are mounting up."
Kinnear, who was speaking to the club's official website, added: "Joey Barton is also missing for about 10 weeks but we have to soldier on and put out the best team we can."
Newcastle signed Bolton midfielder Kevin Nolan on Friday to cover for the loss of Barton, who will have an operation on Friday, and have been linked with a move for Wigan defender Ryan Taylor.
Owen, who has been continually overlooked by England manager Fabio Capello since the Italian succeeded Steve McClaren, left Eastlands on crutches.
Kinnear rues loss of key players
He has scored 10 times this season, though he went into Wednesday's match with only one goal in his last seven matches.
Owen was replaced by Jonas Gutierrez after 19 minutes, while Barton, who was making his first start since November, went off in the second half, with debutant Peter Lovenkrands taking his place.
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