Liam Manning recorded his first victory as manager of the Robins in their 3-2 win against Boro on Saturday, and he will be hopeful that his side can put on a performance at St. Mary's this week.
But, the Robins will have to be at their very best if they're to take anything back to Bristol. Russell Martin's side are currently fourth in the table, six points and seven places above City in 11th.
The Saints are also unbeaten in nine matches, recording six wins and three draws since the end of September.
Remarkably, it will be the first time that the two sides have faced each other in over 10 years, with their most recent battle ending in a 2-0 Saints win in September 2013.
City will again be without Nahki Wells who is still recovering from an ankle injury, as well as Cam Pring who is suspended for the match. However, Joe Williams will be available.
Pring received his fifth yellow card of the campaign against Boro, which leaves Manning with a selection headache as Haydon Roberts is also likely to be unavailable through injury.
Kal Naismith would be the obvious candidate to cover there, however, Mark Sykes has looked assured at right-back in the past and could fill in on the left side. Taylor Gardner-Hickman could also occupy the role.
Here's how I think City will line-up on Wednesday night...