The Lions are four points adrift of safety with two games remaining, but their opponents are also seeking a win to make sure of their playoff place.
With their goal difference comfortably inferior to that of nearest rivals Rotherham United, Millwall need two wins from two or a fortunate Football Association ruling to stay up.
Rotherham are facing a possible points deduction for fielding an ineligible player - Derby loanee Farrend Rawson - in their 1-0 win over Brighton & Hove Albion on Easter Monday.
The FA found last week that the highly-rated defender's youth loan at United had expired and that the paperwork over an extension had not being dealt with correctly. The Millers will learn their fate before this weekend.
Assuming that the Lions are not saved by Rotherham's administrative error, Neil Harris's side have no option but to beat the Rams after failing to pick up maximum points against either Cardiff City or Blackburn Rovers this week.
The blanks fired in those two games are evidence of where Millwall have struggled this season. Only relegated Blackpool have scored fewer times than the Lions, whose top scorer is five-goal winger Magaye Gueye.
Derby's own concerns have been in defensive areas and Harris and his side must exploit that weakness if they are to stand any chance of taking their most recent spell in English football's second tier into a sixth season.
Recent form: DWLWDL
The Rams took the lead at the Galpharm Stadium, but were later salvaging a point with Tom Ince's equaliser after a series of defensive errors that have hindered their promotion push over the last couple of months.
County were right in the mix for a top-two finish until a run of four wins in 15 matches, in which they have kept only three clean sheets.
Their playoff spot briefly appeared to be in jeopardy, but Brentford and Wolverhampton Wanderers dropping points of late leave Derby only one win shy of securing their place in the upcoming lottery for Premier League status.
McClaren will be hoping to get things safely wrapped up with victory at The Den, although mid-table Reading do not pose ominous final-day opponents.
A point this weekend would effectively be enough should both Brentford and Wolves fail to win, with Derby's goal difference better by more than 20.
Recent form: LDWDWD
Harris could name an unchanged side and hope to extract a final couple of goals from veteran striker Ricardo Fuller, formerly of Stoke City and Portsmouth among others.
Millwall possible starting lineup:
Forde; Dunne, Beevers, Nelson, Harding; Abdou, Bailey, Woolford, Gueye; Fuller, O'Brien
Derby possible starting lineup:
Grant; Christie, Keogh, Shotton, Warnock; Dawkins, Hughes, Hendrick, Lingard, Ince; Bent
Head To Head
Millwall have 17 wins compared to Derby's 13 in the history of this fixture, and have avoided defeat in their last two clashes with the Rams.
However, County were 5-1 victors on their last trip to The Den, although none of scorers Bryson, Buxton or Mason Bennett will feature this time around.
We say: Millwall 1-2 Derby
Millwall might get the goal that they have been missing in their last two matches, but keeping Derby out could be a problem. Ince has been on fire for the visitors since joining on loan from Hull City and he could spell curtains for Millwall's survival fight.