Following the striker's goal against Sunderland on Saturday, the Black Cats manager believes he influences his team-mates in a similar manner to the Argentine
The £24 million summer signing has netted 12 goals in 17 Premier League appearances for his new side, including opening the scoring in the 3-1 win over the Black Cats on Saturday.
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Messi scored his 89th and 90th goals of the calendar year on Sunday night against Atletico Madrid to extend his own record, and O’Neill believes Van Persie gives United a similar lift to that of the Argentine at Camp Nou.
"[Van Persie] can get goals out of very little. It looks like nothing is happening, you have players in the area, but all of a sudden he has opened up a gap," O'Neill told reporters.
"Would Barcelona have the same effect if Lionel Messi didn't play? They are a very talented team, but without him you don't know, because Messi is their talisman.
"United have paid close on £30m for a player [£24m] who had just one year left on his contract, so that might tell you how valuable they perceive him. But it's not just the perception, the reality is that he has been fantastic."