Of the 15 who began last Saturday's dour defeat at Bath, only tight-head prop Chris Horsman will run out at Franklin's Gardens as the likes of Ben Gotting, James Brown, Gavin Quinnell, Gary Trueman, Mark Tucker and Miguel Avramovic win starting roles.
"We've had a look at what we've done and obviously we've not played well for any sustained period during our first four matches," Brain says. "This crucial six-match period, with four non-Guinness games, gives us a good opportunity to regroup, look at different personnel and to improve all aspects of our game.
"Some people need a rest because they've played in all four matches, and that does take its toll. It's that, balanced with giving other people an opportunity. To be honest, it's quite an exciting selection."
The break from Premiership competition also provides a chance to step off the yellow card treadmill that's dogged the season so far.
"Some of our sin-binnings have been silly, and some have been questionable," he says, "but they've been a natural by-product of playing on the back foot. What we've got to do now is piece our game together, bit by bit."
Franklin's Gardens has traditionally been a happy hunting ground for Warriors, but Brain knows that, depending on their own selection, Saints are capable of attacking from anywhere on the pitch.
With the prize of Heineken Cup rugby going to the winner of the EDF Energy Cup, and Worcester playing two of their three Pool D games at home, he also knows the value of putting a winning sequence together.
"Northampton is a fantastic stadium, excellent pitch and a good atmosphere. Most teams look forward to going there.
"The competition doesn't matter as much to us as the Guinness Premiership," he says, "but it has an excellent format and we've got to look at it with a real chance to progress to the knock-out stage, which is what we'd like to do."
Team: 01 Tevita Taumoepeau, 02 Ben Gotting, 03 Chris Horsman, 04 Richard Blaze, 05 Phil Murphy, 06 Gavin Quinnell, 07 James Collins, 08 Kai Horstmann (c), 09 Matt Powell, 10 James Brown, 11 Gary Trueman, 12 Simon Whatling, 13 Miguel Avramovich, 14 Mark Tucker, 15 Thinus Delport
Replacements: 16 Lee Fortey, 17 Aleki Lutui, 18 Tim Collier, 19 Drew Hickey, 20 Nick Runciman, 21 Dale Rasmussen, 22 Uche Oduoza