Manchester United 4 Charlton Athletic 0
The 29-year-old Dutch striker was seen leaving the ground just before noon and didn't figure in the final game of the season.
After consecutive goalless home draws, van Nistelrooy's scoring achievements were not needed as the Red Devils romped to victory over a poor Charlton side.
It was manager Alan Curbishley's last game in charge of the Londoners but there was to be no glorious farewell.
Three down by half-time, the Addicks managed only one shot on target and that was a weak effort by substitute Darren Ambrose in the 87th minute.
Youngster Giuseppe Rossi partnered Louis Saha up front and, although they caused Charlton's defence problems throughout, United's star man was Kieran Richardson operating wide on the left.
United had to better Liverpool's result at Portsmouth to clinch second spot and automatic qualification for next season's UEFA Champions League group stage and they started in style.
Cristiano Ronaldo's blistering 35-yard free-kick stung the hands of Charlton keeper Stephan Andersen in the 15th minute and Richardson came even closer to scoring moments later.
Ryan Giggs released him and he raced from midway inside his own half to 30 yards from goal where he fired a shot which came back off the underside of the bar.
United broke the deadlock on 19 minutes when Saha beat Chris Perry to a Giggs corner and headed the ball home from four yards out.
The hosts doubled their advantage four minutes later. Gary Neville floated a 30-yard pass to Giggs on the left and the Welshman cut into the Charlton box before delivering a low cross which was turned in by Ronaldo from close range.
Andersen did well to punch away a powerful Saha drive from the edge of the area before United's third came on 35.
Ronaldo fed Saha down the right and he raced past Gonzalo Sorondo before whipping over a cross from the byline which was turned into his own net by Jason Euell sliding in on the edge of the six-yard box.
England hopeful Darren Bent was gifted a chance in the 42nd minute when he was put in by Mikael Silvestre's suicidal back pass, but he shot wide from 12 yards.
Paul Scholes replaced John O'Shea for United at the start of the second half and, after four months out with an eye problem, it proved a good workout for the former England star.
Scholes sent Richardson racing clear two minutes after the break but he was denied by Andersen's fine save.
But there was no escape for Charlton 11 minutes later. Richardson started and finished a glorious move when he robbed Radostin Kishishev on halfway before racing on to score with a superb shot.