That means the starting team has a somewhat youthful slant to it with Saints coach Wayne Smith drafting in Academy products Ian Vass, Darren Fox, Dan Richmond, Mark Tucker and Robbie Morris to face the West Country team.
Players not available for selection were fullback Nick Beal and lock Matt Lord, both picking up injuries against Toulouse but likely to be fit for Sunday's game against Newcastle, and centre Chris Hyndman, who suffered concussion on Saturday and will be out for three weeks.
Wednesday's game will mark Richmond's last match for the club before he has knee surgery on Thursday morning, which will keep him out of action for the remainder of the season.
Nearly 8,000 tickets have been sold for Saints’ first midweek game of this season but the club is also expecting plenty of other spectators to turn up on the day.
Smith said: "The losses at Twickenham and Toulouse have increased the importance of Wednesday night's match against Bristol.
"We have to win the remaining Zurich Premiership matches to give ourselves a chance of appearing in Europe again next year."
Northampton Saints: 15 Bruce Reihana, 14 Jon Sleightholme, 13 Mark Tucker, 12 John Leslie (captain), 11 Oriol Ripol, 10 Paul Grayson, 9 Ian Vass, 8 Andrew Blowers, 7 Budge Pountney, 6 Darren Fox, 5 Steve Williams, 4 Jon Phillips, 3 Robbie Morris, 2 Dan Richmond, 1 Tom Smith.Replacements: 16 Steve Thompson, 17 Matt Stewart, 18 Rob Hunter, 19 Grant Seely, 20 Matt Dawson, 21 Peter Jorgensen, 22 Ben Cohen.
Kick-off: 20.00 BST (19.00 GMT)