Steve Harper admits Newcastle's depleted squad is being severely tested during the Premier League run-in.
The Magpies enjoyed a 4-1 win over Wolves at St James' Park last week despite having seven players out injured.
But the absence of three key players proved too much on Sunday as they lost at Aston Villa.
Midfield pair Kevin Nolan and Cheick Tiote were suspended while striker Shola Ameobi was ruled out with a knee injury.
Ameobi was set for a scan on Monday and should he be sidelined for the season then Harper concedes it will be heavy going for Alan Pardew's men.
"When you take three massive players out of the heart of your team, it is going to be to the detriment of the team," he said.
"To be without Kevin Nolan and Cheick Tiote was massive for us - but losing Shola overnight was one too many.
"Suspensions and injuries are killing us. We knew we had a small squad and that's why last week (against Wolves) was a massive result."
Newcastle have just over a week to rest and recuperate before they host Manchester United next Tuesday, for which they will welcome back at least Nolan and Tiote.
The Premier League leaders have a UEFA Champions League clash against Chelsea and an FA Cup semi-final against derby rivals City to contend with before then.
And Harper hopes the Red Devils' demanding schedule does the injury-hit Magpies a favour.
"We've got to hope the two big games take a lot out of them this week because they are flying in the league," he added.
"It will be a very tough game for us but hopefully they will have two tough games this week and we will have 52,000 roaring us on and a few first-choice bodies back out there."