However, with their opponents coming off the back of four consecutive league wins, the Azoreans will face an uphill struggle at the Estadio de Sao Miguel.
A bit of a mismatch on paper, Santa Clara boss Daniel Ramos will undoubtedly be looking to inflict a major upset on league heavyweights Benfica.
In order to achieve that though, Ramos will have to depend on a faltering attack that has not found the back of the net since the team's last league win in early December.
To make matters worse for the Azoreans, the team will also be without their talismanic striker Thiago Santana, after the 27-year-old completed a move to Shimizu S-Pulse.
Thiago Santana scored eight goals in 10 games for the Ponta Delgada outfit this season and his attacking prowess will be sorely missed by many at the club.
However, the loss of Santana will not be the only thing giving Ramos sleepless nights. His side have some of the worst home form in the league this season, having collected just four points from a possible 15 at the Estadio de Sao Miguel.
Benfica, on the other hand, have picked up almost as many points on their travels as they have at home this season and manager Jorge Jesus will certainly be looking to etch out his side's 10th league win.
The Eagles managed to put their Portuguese Super Cup woes to bed with a 2-1 win in the league against Portimonense last time out, keeping them within touching distance of league-leaders Sporting Lisbon.
A last-minute own-goal from Gilberto Moraes Junior dashed Benfica's hopes of picking up their fifth clean sheet of the season.
Santa Clara Primeira Liga form: WLLWLL
Benfica Primeira Liga form: LLWWWW
Benfica form (all competitions): DWWWLW
Despite losing their midweek clash against Moreirense, Ramos will be pleased that his side managed not to pick up any major knocks or injuries.
Following the sale of Thiago Santana, Ramos will likely call upon Shariar Moghanlou to lead the line again for the Azoreans.
Santa Clara possible starting lineup:
Marco; Villanueva, Fabio Cardoso, Afonso; Sagna, Carvalho, Rashid, Costinha, Ukra; Carlos, Moghanlou
Benfica possible starting lineup:
Vlachodimos; Gilberto, Ferro, Vertonghen, Alex Grimaldo; Silva, Weigl, Taarabt, Everton; Nunez, Waldschmidt
We say: Santa Clara 0-3 Benfica
With Thiago Santana no longer pulling the strings at Santa Clara, it is difficult to see how Ramos's men will prevent Benfica from picking up their fifth league win on the bounce, and we think the Eagles will do it in style.