The hosts' struggles continued with a slender loss to Northampton Town on Saturday, while the Millers succumbed to a first-minute goal against promotion-chasing Wrexham.
Match preview
Fresh from a first win in five games on October 8 - a penalty shootout success over Colchester United in the EFL Trophy - Leyton Orient returned to losing ways at the weekend, where a solitary Cameron McGeehan effort was enough to propel Northampton to victory.
On the balance of possession and overall play, Leyton Orient would have been worthy of one point and potentially all three, but Richie Wellens's side were found wanting in the final third as they fell to their third straight loss in the third tier.
The month of Halloween has indeed been a horror show for the O's, who have also fallen to one-goal losses to Exeter City and Lincoln City over the past three weeks and are hovering dangerously close to the trapdoor in 20th place in the League One table.
As well as going down in each of their last three league affairs, Wellens's out-of-sorts troops have now failed to win in five - also playing out back-to-back draws with Peterborough United and Wrexham in September - and their two-year stay in League One is already under serious threat.
Home is not where the heart is for Tuesday's hosts either, as Leyton Orient have failed to win any of their last seven League One matches at the Gaughan Group Stadium while only prevailing in one of their last 11 in total, a 3-1 beating of Cheltenham Town in April.
As Leyton Orient's miserable streak continued on October 19, Rotherham United found themselves on the wrong end of the scoreline for the first time in six matches, as Paul Mullin's 16th-second strike proved decisive at the AESSEAL New York Stadium.
Similarly to Leyton Orient against Northampton, Steve Evans's side had opportunities of their own to glean at least a share of the spoils, but a lack of ruthlessness let them down as they were subjected to their first defeat in any competition since September 21.
The Millers had taken a respectable eight points from an available 12 before Saturday's setback, who sit four places and six points better off than Leyton Orient in the standings in 16th place, only four points off the playoff positions at this embryonic stage.
A four-game unbeaten run on the road in League One also stands the Millers in good stead for Tuesday's game, even if three of those contests have ended in draws and their solitary victory coming against second-from-bottom Cambridge United.
The midweek showdown will end a 10-year gap without a competitive meeting between Leyton Orient and Rotherham, who have not crossed paths since the 2013-14 League One playoff final, which the Millers won on penalties following a 2-2 stalemate at Wembley.
Leyton Orient League One form:
W
D
D
L
L
L
Leyton Orient form (all competitions):
D
D
L
L
W
L
Rotherham United League One form:
L
D
W
W
D
L
Rotherham United form (all competitions):
D
W
W
W
D
L
Team News
One positive from Leyton Orient's loss to Northampton was the fact that no new O's players came off with injuries, although right-back Tom James is now one booking away from a one-game suspension in the third tier.
Wellens may not see much need to make significant alterations to his starting lineup - unless jellied legs play a part - but Tottenham Hotspur loanee Jamie Donley and 39-year-old skipper Darren Pratley are options for change.
Similarly, Rotherham also came out of the weekend's loss unscathed, although Jonson Clarke-Harris missed that encounter due to the hamstring problem he picked up against Peterborough United earlier this month.
Evans has conceded that Clarke-Harris is unlikely to be back in action until the middle of November, so Sam Nombe and Jordan Hugill will scrap it out to lead the line; the former got the nod for the Wrexham defeat and played the full 90.
Left-back Reece James was substituted after just 55 minutes on Saturday, but a lack of alternative wide defensive options should see the 30-year-old retain his place.
Leyton Orient possible starting lineup:
Keeley; James, Beckles, Happe, Currie; Ball, Brown; Graham, Galbraith, Agyei; Donley
Rotherham United possible starting lineup:
Dawson; Rafferty, Humphreys, McCart, James; Tiehi, Powell; Wilks, Odoffin, Bramall; Nombe
We say: Leyton Orient 0-1 Rotherham United
The absence of Clarke-Harris means that Rotherham lose their chief goalscorer, but the Millers could very well have got something from their game against Wrexham had they been a touch more clinical.