Midfielder Moussa Sissoko is the latest to succumb after suffering a hamstring strain at Southampton last weekend, and he joins keeper Tim Krul, full-back Mathieu Debuchy and striker Loic Remy on the sidelines.
With Yohan Cabaye, whose goal secured a first league win at United since 1972 before Christmas, having been sold to Paris St Germain in January, that robs Pardew of almost half the team which started that day.
The 52-year-old said: "We have got a real injury crisis at the moment. We lost Moussa this week in the Southampton game, so of the team that started when we beat Manchester United, five won't play through injury.
"Moussa has a hamstring strain, and we think that's at least two to three weeks."
Pardew had hoped to have Remy back from a calf problem this week, but he will remain sidelined along with Krul (shoulder) and Debuchy (groin).