Leaders Gloucester's home game against second-placed Leicester - a repeat of last year's Premiership final - has been brought forward from next month because of the Tigers' involvement in the EDF Cup semi-finals.
Both teams will go into the crucial contest in a rich vein of form, with just one defeat in each of their last five Premiership matches, but with depleted line-ups.
Gloucester, who enjoy a four-point lead at the halfway stage of the regular season, have home advantage as they look to avenge their 44-16 defeat at Twickenham last May as well as a 30-17 reverse at Welford Road in October.
Dean Ryan's men are unbeaten in their last 22 games at home in all competitions but they will be without a host of players through injury or international duty.
Because the Premiership take precedence over England Saxons, at least Leicester will be able to call on Jordan Crane, Ollie Smith and, injury permitting, Tom Varndell, who all helped to destroy Ireland A last weekend, but exciting Fijian Seru Rabeni is out through suspension.
Tigers' Argentinian prop Marcos Ayerza, who has been in impressive form since returning from World Cup duty, is warning his team-mates to expect a tough challenge from the league leaders.
"It's going to be a massive game," he said. "Gloucester have proved to be a very strong side in the last couple of years.
"I remember the league games against them last year when we didn't beat them home or away so we know it's going to be a big challenge for us, having so many players out with the Six Nations and injury.
"It will be a very tough game but we are prepared for that. If we do our own things well, then I believe we can beat anyone in the Premiership on the day.
"We want to have a big performance and gain some sort of revenge for the loss against them at Welford Road."
Saturday's game is one of three brought forward from March 22 because of the EDF Cup. On Sunday, Saracens take on Worcester at Vicarage Road, while Wasps and Sale meet at Adams Park.