Can Sheridan's men upset Boro's beleaguered squad?
These two sides may be two leagues apart and have a huge gulf in quality among the players but this is by no means a guaranteed result.
Chesterfield (2/1) won their opening home league match and fans will be hoping to see more of the same at their new ground.
After so much hype and expectation around Middlesbrough (Evens) this season, fans were bought crashing back to the real world after Roy Keane's Ipswich side thumped them 3-1 in their opening match of the season.
Despite Scott McDonald's first-half goal, Middlesbrough's new signings failed to shine and their opponents highlighted the need for more faces before the Teessiders are able to seriously challenge for promotion.
In this match they will be without their boys from north of the border as Kris Boyd, Stephen McManus, Barry Robson and Kevin Thomson are all on international duty as is Estonian winger Tarmo Kink.
They are also without midfielder Willo Flood who was stretchered off in the league match on Saturday and Gary O'Neil's future is still under the spotlight as he sits out through injury.
Boro will be hoping Australian Scott McDonald can make it two in two, and looks a good price to score first at 6/1 or 6/4 at any time.
Leroy Lita should also be pushing for a start, he had an impressive pre-season and is always a threat in front of goal and is 5/1 to score first.
For an outside bet, I would certainly look towards Nicky Bailey. At 11/1 he provides some good value to score first as the ex-Charlton captain has a decent scoring record for a midfielder.
With their squad so thin and devoid of the usual first-team names, I am wary of tipping them and would be more tempted by betting on Chesterfield draw no bet at 7/4.
Boro have historically struggled away at lower-league grounds in cups and the 2004 Carling Cup winners are without a win in nine away matches in all competitions.
New Chesterfield signing Craig Davies is suspended after being sent off on his debut against Barnet on Saturday. Ian Morris is an injury doubt after limping off in that match too so the League Two side have their own selection problems.
Chesterfield boss John Sheridan knows how to do well in this cup after actually scoring the winning goal in 1991 League Cup final for Sheffield Wednesday against Manchester United.
Jack Lester is favourite to score first for the home side, he has been prolific in his three seasons there so far and is a real favourite among the fans and is 15/2 to score first.
With morale possibly low among the remaining Boro players I think the 10/1 on a 1-0 Chesterfield win is a decent price.