Shahzad underwent a scan in Sydney today which revealed a minor tear in his hamstring and while he will miss the final two games of the already-lost series, he is expected to be fit in time for the World Cup.
The Yorkshireman will remain with the England squad in Australia to begin his rehabilitation but it is a further blow to England's World Cup attack.
Spinner Graeme Swann (back/knee) and Tim Bresnan (calf) were forced to leave the tour early last week while Stuart Broad is still recovering from the stomach injury he suffered during the Ashes.
All four are expected to be fit in time for the start of the World Cup though, with Broad revealing yesterday that he was ahead of schedule in his return.
Broad is hoping to make his return after two months out of action for England's first warm-up match against Canada on February 16.
Fellow quick Chris Tremlett was also ruled out of tomorrow's sixth and penultimate one-dayer in Sydney after he also had a scan on a side strain today, although he was cleared of suffering a tear to a side injury.
The tall right-armer will be reassessed in the coming days and may be fit to return to action for the final game in Perth on Sunday.
"Shahzad has suffered the type of minor hamstring tear that required at least eight days of rest, and as such he will be rested," an England and Wales Cricket Board spokeswoman said.
"He will remain with the England squad in Australia where he will be in the best to begin his rehabilitation from the injury.
"The England team are remaining cautious with Tremlett (who is not a part of the World Cup squad) despite the scans showing no sign of a tear.
"The specialists will take another look at him in the coming days and make a further assessment before the final game of the series in Perth on Sunday."
England's batsmen will be aiming to put a disappointing one-day international series behind them, and re-establish their dominance over Australia this winter, when they play the first of two dead rubbers in Sydney tomorrow.
After conceding the seven-game series with a 51-run defeat in Brisbane on Wednesday, skipper Andrew Strauss admitted that his batsmen had let the side down.
England have failed to find the consistency with the bat that marked their Ashes success earlier in the tour as they have been bowled out in all four of their defeats.
The tourists' only success so far arrived in Adelaide when a century from Jonathan Trott guided them to 299 for eight - England's highest score against Australia on their home soil.
Strauss has repeatedly lamented "soft dismissals" for his side's problems and with the World Cup looming large there is little time left to rectify the issue.
With that in mind all-rounder Luke Wright admitted that England had plenty of incentive in the remaining two matches of the series, which concludes in Perth on Sunday, as they aim to go to the sub-continent with some improved form under their belt.
"It has been disappointing series, but no-one knows that more than the batters - we want to put it right," he said.
"It showed in the one game we won, when Trotty went on and made a big hundred. That's what we did well in the Test matches, people got big hundreds and that's why we won the series.
"We've played outstandingly well in one-day cricket for two years now, so very disappointed to lose the series but obviously we've still got a lot to look forward to.
"The next two games are very important for us going into the next World Cup.
"It's a massive confidence game and any momentum we can get going into that World Cup is going to be a help.
"If we can go home and it's 4-3 then we can take quite a lot from that. Australia are such a top opponent, especially here as well." The 25-year-old all-rounder has been a regular part of the England limited overs squad for the past couple of years without pinning down a set role with either bat or ball.
His bits-and-pieces role has been underlined in the already-lost series against Australia during which he has played just one game - when he was the second top-scorer with 32 in last week's defeat in Sydney.
Wright is, however, likely to return on the same ground tomorrow following the mounting injury count to England's bowlers.
In their absence Wright, who bowled only two overs in his one match in the series, is likely to be given a more significant role with the ball and he is hoping to grab his opportunity as time ticks down toward the World Cup.
"Every time you play you give yourself an opportunity to make a statement and keep your spot," he said.
"It only takes one game, a big hundred or a five-for to get a spot down.
"I've played just the one game but I've trained hard and I'm hoping to get the nod for tomorrow.
"All you can do is work hard and when you get your chance take the opportunity.
"You've always got a lot to prove in international cricket. It doesn't take long for everyone to need a performance and you always want one."