A litany of mistakes in the opening half had the Tigers leading 28-6 and the game seemily over by the 30th minute. A third James Hook penalty left Ospreys trailing by 19 points at the break but whatever Lyn Jones said to his players at half-time certainly had the desired effect.
They came scorching back into the game with tries from wing Shane Williams (2) and full-back Lee Byrne before the Tigers again extended their lead with a Tom Varndell try.
Nikki Walker then scored his side's fourth try to leave Ospreys trailing by five points but try as they might they could not peg back the lead.
It was a brave attempt but this victory once again pointed up the power of this Leicester squad and whatever about their Premiership ambitions, it is going to take a massive effort by whoever hopes to derail their bid for the Heineken Cup.
Meanwhile in a dress rehearsal for next weekend's Heineken semi-final Northampton were beaten 35-29 by London Wasps, a defeat that edges the Saints ever closer to relegation. To compund their misery they lost out-half Carlos Spencer with an ankle injury that looks certain to rule him out of that match.
Leicester Tigers: 15 Sam Vesty, 14 Tom Varndell, 13 Dan Hipkiss, 12 Daryl Gibson, 11 Alesana Tuilagi, 10 Paul Burke, 9 Harry Ellis, 8 Martin Corry (captain), 7 Shane Jennings, 6 Tom Croft, 5 Ben Kay, 4 Leo Cullen, 3 Julian White, 2 George Chuter, 1 Martin Castrogiovanni.
Replacements: 16 Gavin Hickie, 17 Alex Moreno, 18 Louis Deacon, 19 Brett Deacon, 20 Frank Murphy, 21 Andy Goode, 22 Geordan Murphy.
Ospreys: 15 Lee Byrne, 14 Shane Williams, 13 Sonny Parker, 12 Andrew Bishop, 11 Nikki Walker, 10 James Hook, 9 Justin Marshall, 8 Filo Tiatia, 7 Jonathan Thomas, 6 Ryan Jones, 5 Alun Wyn Jones, 4 Brent Cockbain, 3 Adam Jones, 2 Huw Bennett, 1 Duncan Jones (captain).
Replacements: 16 Barry Williams, 17 Paul James, 18 Mike Powell, 19 Richard Pugh, 20 Jason Spice, 21 Shaun Connor, 22 Stefan Terblanche.
Referee: Alan Lewis (Ireland)
Touch judges: Simon McDowell (Ireland), Peter Fitzgibbon (Ireland)