The Valiants are languishing in 23rd position in the League One table, while the O's will begin the midweek contest in 10th position.
Match preview
Leyton Orient's hopes of achieving a playoff finish have been dented by consecutive 1-0 defeats to Bristol Rovers and Wigan Athletic.
Saturday's away meeting with the Latics was goalless until Jason Kerr netted a 73rd-minute winner to leave the O's with nothing to show for their efforts after they had played the entire second period with 10 men following Ethan Galbraith's 43rd-minute red card.
Having failed to take anything from their last two games, 10th-placed Leyton Orient are now left eight points adrift of the top six.
Leyton Orient now quickly turn their focus to Tuesday's fixture, where they will have the chance to complete a league double over Port Vale after recording a 1-0 win when the two sides met last month.
The O's have managed to avoid defeat in each of their last seven home games against the Valiants, although they have had to settle for a point in each of their previous three head-to-head home matches.
Darren Moore is still searching for his first win as Port Vale boss, having taken just one point from his six matches in charge.
Baylee Dipepa's second-half effort proved to be a mere consolation in Saturday's 2-1 loss against Shrewsbury Town, leaving them without a win in 12 matches.
Although they boast at least one game in hand over the teams above them, Port Vale have their work cut out to remain in the third tier with a sizeable seven-point gap separating them from safety.
Having conceded at least two goals in each of their last seven outings, the Valiants know they need to improve defensively if they are to have any hope of extending their stay in League One into a third season.
Incidentally, Port Vale have not kept a clean sheet since their most recent win, which took place against Blackpool at the end of December.
Leyton Orient League One form:
W
L
W
W
L
L
Port Vale League One form:
L
L
L
D
L
L
Team News
Leyton Orient boss Richie Wellens is contending with an injury list which includes Dan Agyei, Jordan Graham, Theo Archibald and Adam Thompson.
Centre-back Dan Happe is also expected to be unavailable after missing the last six matches with an injury issue.
Rob Hunt is set to replace the suspended Galbraith, and there could also be a place in the starting lineup for Jordan Brown after he dropped down to the bench at the weekend.
As for the Valiants, they are likely to be without Ryan Loft and Dan Gore, while Uche Ikpeazu remains a long way off from returning to action following a shoulder problem.
Dipepa could be presented with a starting place after he came off the bench to score his first senior goal in Saturday's defeat.
Alex Mighten played the final half-hour against Shrewsbury, and the Nottingham Forest loanee is now in contention to start on Tuesday.
Leyton Orient possible starting lineup:
Brynn; Hunt, Beckles, Cooper, James; Brown, El Mizouni; Forde, Sanders, O'Neill; Sotiriou
Port Vale possible starting lineup:
Ripley; Debrah, Smith, Jones; Sang, Ojo, Garrity, Mighten; Weir; Dipepa, Wilson