Chesterfield lost out to a single goal at Luton Town, scored by Danny Hylton in the 53rd minute at the time when the visitor's were enjoying a solid, attacking spell.
A quick ball from inside their own half released the scorer to cut in from the left and drill the ball in low at the far post.
Luton had to play the final phase with ten men after Pelly-Ruddock Mpanzu was red carded for a foul on Andy Kellett quarter of an hour from time.
With Bradley Barry suspended and top scorer Kristian Dennis benched, caretaker boss Guy Branston drafted in Matt Briggs and Chris O'Grady and he lined up with a 4-2-3-1 formation, Robbie Weir and Jordan Flores given the holding roles.
Ahead of kick-off, Branston, who'd been on the pitch throughout the warm-up routine, went to chat with the travelling fans to ask their views on the team he'd selected, something that seemed to go down well.
Luton came out of the traps the quicker and rapidly saw a Hylton header and a Luke Gambin shot go close ahead of Spireites first real effort, a Sam Hird looping shot.
Hatters' skipper Scott Cuthbert had a couple of headers blocked whilst Spireites saw Louis Reed and Andy Kellett both find the keeper from excellent positions. Briggs hit a couple of long rangers ahead of the hosts enjoying a long spell of pressure as half-time beckoned, a Mpanzu stooping header from an inch perfect cross from Gambin glancing wide from the best opening of the first half.
Spireites started the second half well but were sucker punched when Hylton scored.
Louis Reed and Kellett saw efforts to close and crosses in from O'Grady and Briggs were deliciously inviting but no-one could get a toe onto them.
After the dismissal, Luton dealt with the situation extremely well and Collins, three times and sub Harry Cornick missed sitters as they frequently broke forwards whilst 20-odd yarders from Weir and Jack McCourt were Chestefield's closest calls.
Plenty of effort and endeavour, but another Spireites loss making the two home games next week, against Yeovil and Cheltenham both vital.
Luton Town: Stech, Potts, Cuthbert, Stacey, Lee (Cornick 73), Hylton, Shinnie (Cook 21), Mpanzu, Collins, Gambin (Rea 66), Sheehan.
Subs (not used): Shea, Justin, Senior, Jarvis.
Goal: Hylton 53
Chesterfield: Anyon, Wiseman, Hird, Jules, Kellett, Weir, Briggs, Flores, Reed, O'Grady (Ugwu 73), De Girolamo (Mitchell 68),
Subs (not used): Lee, Dennis, Dimaio, Brewster.
Ref: Charles Breakspear
Bookings: Hird (Chesterfield), Sheehan (Luton)
Sending-Off: Mpanzu 73, serious foul play
Attendance: 7575 (310 from Chesterfield)