Fulham and England striker Zamora suffered a nasty break just above his ankle in a challenge with Wolves' Karl Henry and is expected to be out for five months.
As a result you should look to bring in team-mate Moussa Dembele, who has plenty of goals in him - hitting a winning brace after Zamora's injury. The Belgian will lead the line against Blackburn as Fulham seek to snap their away jinx.
Manchester United's Ecuador winger Valencia suffered a sickening ankle fracture and dislocation while on Champions League duty against Rangers.
He will be out for most of the season, according to United.
But Tottenham's Aaron Lennon is back and costs a similar amount, while Valencia's United team-mate Nani could well profit if you have a spare few million quid lying about.
Other news sees some Fantasy stalwarts return from injury.
Mark Schwarzer, the Fulham keeper, is back after featuring ahead of schedule against Wolves and is a good tip to keep a clean sheet.
John Terry and Branislav Ivanovic returned for the Champions League win over Zilina and given the way Chelsea are playing, expect them to keep clean sheets in what could be a big win against Blackpool.
Similarly, Didier Drogba got a night off after being suspended in midweek, so he should lead the line against the Tangerines. Frank Lampard is 50-50 but don't expect him to be risked against Ian Holloway's minnows.
Suspensions-wise, Liverpool winger Joe Cole returns from a three-match ban picked up on his league debut for the club. Provided nothing happens to him in the Europa League match against Steaua Bucharest he will start against Manchester United.
Bolton's Gary Cahill joins keeper Jussi Jaaskelainen on the sidelines as he starts a three-match ban, while Lee Cattermole sits out two games after getting his second red card of the season.
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Here are the injuries and suspensions for week five of the season:
- Bobby Zamora
- Antonio Valencia
- Manchester United