A place in the fourth round of the FA Cup sealed, Liverpool returned to league duties away to arch rivals Manchester United.
Some surprises in the lineup saw the inclusion of Downing in a front trio with Sterling and Suarez meaning new signing Sturridge and the fit-again Borini began on the bench.
Both teams started well but it took until the 19th minute for a breakthrough and it came for the home side as an Evra cross looped in and found Van Persie who side-footed past Reina to give United the lead.
The lead could have been doubled within minutes as Van Persie scooped his shot over after being put through on goal by Young.
An amazing block from Agger denied Welbeck after a horrific giveaway by Allen gifted United possession on the edge of the area and Cleverley volleyed wide before a goalmouth scramble saw Skrtel clear the danger by hacking Van Persie's shot off the line but in the melee, a coming together between Kagawa and Reina left the Liverpool keeper injured but able to continue after a short delay which soon saw the whistle for the end of the first half.
Liverpool needed a change and it came with the introduction of Sturridge in place of Lucas and the swap let to a massive change in the Liverpool attack and in the 52nd minute, Liverpool had their first attempt on goal in the game as Suarez teed up Wisdom who shot off target.
Wisdom's miss was soon proved costly as United extended their lead as Van Persie looped in a free-kick which found the unmarked Evra at the back post who headed home with the final touch coming off Vidic.
Borini came on to replace Sterling in a change which had been planned before Sturridge had scored and the Liverpool hopes were alive as Sturridge and Borini both went close but they were unable to breach the defence as United held on for the win.
Next up is the hosting of Norwich on Saturday in a game that surely should end with a Liverpool win but many will remember that after the 5-2 demolition of the Canaries in the previous meeting they went on a stellar unbeaten run and currently sit five points behind their opponents.