Plymouth’s lead at the top was cut to two points at the weekend following their home defeat to Devon rivals Exeter.
Now the Pilgrims will be hoping to hit back when they welcome a Leyton Orient side who occupy the final play-off spot and boast the league’s top goalscorer in Jay Simpson (13 goals).
After getting one over their fierce rivals, Exeter now make another tough trip to sixth placed Mansfield.
The Stags have lost two of their last three matches and will be wary of a Grecians side which also beat Portsmouth on the road this term.
Hot on Plymouth’s tail are Oxford United, who have lost just twice all season in the league.
Michael Appleton’s side face Newport County, who completed their third draw in as many games when they played out a goalless stalemate with fellow strugglers Yeovil at the weekend.
In the third and final automatic promotion spot, Northampton Town, who have been boosted buy the news that Kelvin Thomas has reached an agreement to buy a controlling stake in the club, make the trip to Crawley.
The Cobblers have lost just once in their last 12 outings but play a Crawley side which scored two early goals to sink Bristol Rovers on Saturday to stretch their unbeaten run to four matches.
Accrington Stanley, in fourth, also extended their unbeaten run to four games when they edged a five-goal thriller with Cambridge at the weekend.
Now John Coleman’s side could move up to third if they extend that run to five games against a Hartlepool side who were beaten for the third time in four games at Mansfield last time out.
Portsmouth’s form has dipped lately; they are without a win in five and as a result have dropped out of the automatic promotion places.
Paul Cook will be hopeful of stopping his side’s rot against Jackie McNamara’s York team, who are one point above the bottom-two and last tasted League Two victory back in early September.
Yeovil are without a win in 10 and could drop to bottom if Dagenham & Redbridge win away at Wimbledon.
The Glovers play League Two’s joint tightest defence with Gareth Ainsworth’s Wycombe side having only conceded 14 goals all term.
They will be looking to get back to winning ways after a 91st minute equaliser denied them three points against Wimbledon on Saturday.
The Dons have made a surge towards the play-off places lately, picking up 11 points from their last five games.
All League Two Matches:
Accrington Stanley v Hartlepool
AFC Wimbledon v Dagenham & Redbridge
Bristol Rovers v Stevenage
Crawley v Northampton
Luton v Carlisle
Mansfield v Exeter
Morecambe v Cambridge
Notts County v Barnet
Oxford v Newport
Plymouth v Leyton Orient
Portsmouth v York
Yeovil v Wycombe