The hosts will be looking to end a run of five consecutive league defeats, while a 5-1 victory last time out has lifted Santa Clara to seventh spot, level on points with Saturday's opponents.
Vitoria de Guimaraes come into this game on the back of five consecutive defeats in the Portuguese top flight.
Last time out, Os Vimaranenses suffered a disappointing 3-0 defeat at the hands of Portimonense, as Lucas Possignolo, Dener Clemente and Beto all got on the scoresheet in a dominant win for the hosts.
That stretched their losing run to five games, a run which has seen them fall well behind the Primeira Liga's top five.
As a result of their poor run, manager Joao Henriques was dismissed, and the side will now begin life without him at the helm.
They will look to reverse their fortunes on Saturday, and put some distance between themselves and the sides below them, as they welcome Santa Clara who sit level on points with them.
Daniel Ramos's side recorded a dominant victory last time out, as they hosted basement side Nacional.
Before that, Ramos's men looked set to see out a commendable 1-1 draw with second-placed Porto to continue their impressive run, until Antonio Martinez netted a winner for the defending champions in the 95th minute of the game.
Despite that disappointing late defeat, Santa Clara have enjoyed a rise up the Portuguese top flight recently, now sitting level on points with Saturday's opponents.
As a result, Ramos will be keen to record an important victory away from home, as that would see them leapfrog the Guimaraes outfit and break into the top six.
Vitoria de Guimaraes welcomed midfielder Pepelu back to action last time out following his suspension.
They opted for a different shape for that game against Portimonense, changing to a back three and a front three.
The line will be led by Oscar Estupinan, who has shown some clinical form this campaign, netting eight goals in 15 league games.
Rui Costa will lead the Santa Clara line with confidence, having netted a brace in the dominant 5-1 victory last time out.
Their only absentee should be midfielder Julio Romao, who remains out with a knee injury.
Vitoria de Guimaraes possible starting lineup:
Varela; Fernando, Amaro, Mumin; Sacko, Pepelu, Andre, Mensah; Edwards, Estupinan, Rochinha
Santa Clara possible starting lineup:
Marco; Ramos, Cardoso, Villanueva, Mansur; Morita, Lincoln, Carvalho; Carlos, Costa, Crysan
We say: Vitoria de Guimaraes 1-3 Santa Clara
The two sides come into this game in opposite runs of form, and we see Santa Clara sealing another victory following their dominant win last time out.
Despite Vitoria's quality, they have struggled to click in recent weeks, and look to be limping towards a poor end to the campaign.