Both sides find themselves in the bottom half of the table after a mixed start to their respective third tier campaigns.
Marvin Bartley’s Doonhamers have lost their last five in all competitions, but they will have a boost in confidence following a much-improved performance on Saturday in their cup defeat to Arbroath.
Meanwhile, the Black and Golds return to action recharged and raring to go after a weekend off.
So far, Peter Murphy’s men have been unable to take any points from the league’s full-time teams, but they have yet to face any of them on home turf.
Queens claimed the bragging rights back in August at Palmerston as they ran out 3-1 winners.
However, Annan fans will be confident of a different result this time round and the string of former Palmerston players wearing black and gold will be up for the challenge.
A large crowd is expected at Galabank for Saturday’s derby clash as the Black and Golds look to take their first points off of one of the league’s full-time outfits.
Murphy added: “I’m looking forward to it and the players are desperate to get back after a week off.
“A few of the lads have got ties to Queen of the South and they will be desperate to play and do well.
“From my point of view I just want us to start the second quarter right and give ourselves a chance and an opportunity to pick up some points as it’s a bit tight at the minute with the four or five teams around us.
“I think in the first quarter against the four full-time teams we haven’t picked up any points so that’s something we’re looking to change.”
The visitors have lost their last five in all competitions, but Murphy’s full focus is on his Annan squad, he said: “Queens can look after themselves, we’ll just concentrate on what we’re doing and we’ll see how well we can do on Saturday.
“It’s another game, it’s a good challenge and it’s a good opportunity. We’ll see how we get on.”
At the quarter-season review on Tuesday night, the Annan chief noted the areas in which his side need to improve if they are to start climbing up the table.
Murphy said: “We didn’t start very well and that was down to the injuries that we had. We played Falkirk who have started their season very strongly, and we played them away from home with no recognised centre forward.
“We have conceded too many early goals in too many games. I think out of four games in the first nine we’ve conceded in the first ten minutes, so that’s something that needs to change.
“It’s been a wake up call for our players but certainly something that we feel once we improve then it will give ourselves a chance because we finish games very strongly.
“When we did our first quarter review with the players on Tuesday night, I looked back at our first quarter review of last season and it was the same sort of things.”
Meanwhile, under pressure Bartley believes his injury-hit side showed positive signs during their 2-1 SPFL Trust Trophy defeat to Arbroath.
And he is hoping the Doonhamers’ fortunes can turn in an important derby match.
Bartley said: “It’s a massive game and people will say it’s only three points but we want the bragging rights for the fans. We will go out there and deal with the 90 minutes.
“We know it’s a big game and we’ve put an expectation on ourselves to go out there and win.”
Bartley expects to have Gavin Reilly, Lee Connelly and Craig McGuffie to be back in the squad after their spell on the sidelines. Also, Oscar MacIntyre and Alex Ferguson will be back after being cup-tied last week.