Reeling from their Taca da Liga exit last time out, both sides will head into the midweek clash looking to secure a positive result in their first meeting since claiming promotion from the Segunda Liga last season.
Match preview
Nacional suffered a second cup exit within the space of nine days as they were beaten 3-1 by 3-1 by high-flying Sporting Lisbon in the opening round of the Taca da Liga last Tuesday.
With nothing to separate the sides in the first half, Morten Hjulmand and Viktor Gyokeres scored in an eight-minute spell to put the hosts two goals up, and after Ruben Macedo pulled one back in the 66th minute, Gyokeres netted his second in the 70th minute to see off a comeback scare.
Nacional have now gone six consecutive games without a win, claiming one draw and losing five, including a somewhat disappointing 2-1 defeat against Segunda Liga outfit Uniao Leiria in the Taca de Liga third round on October 20.
Tiago Margarido's men secured a second-placed finish in the Segunda Liga last season to end their three-year absence from the top flight, but have failed to win eight of their nine matches since their return, losing five and claiming two draws so far.
The Alvinegros have picked up just five points from their eight Primeira Liga matches so far to sit bottom but one in the standings, just one point above last-placed Farense, albeit with one game in hand.
While Nacional will be looking to stop the rot and get their season up and running, next up is the challenge of an opposing side unbeaten in nine of their last 10 clashes, claiming six wins and three draws since December 2017.
Like the hosts, Santa Clara were also dumped out of the Taca da Liga in the opening round as they suffered a 3-0 defeat against Benfica when the two sides squared off at the Estadio da Luz in midweek.
Santa Clara did well to keep the scores level in the first half, but Angel Di Maria broke the deadlock with a vicious strike in the 71st minute before Greek Vangelis Pavlidis scored a brace to send Benfica through to the semi-finals.
Prior to that, Os Acorianos booked their spot in the fourth round of the Taca de Portugal courtesy of a 1-0 victory over Gondomar on October 19, one week before seeing off Gil Vicente 2-1 in the league thanks to goals from Sidney Lima and Diogo Calila.
Having gained promotion from the Segunda Liga last season, Santa Clara men have been impressive on their return to the Primeira Liga, claiming six wins and three draws from their opening nine matches.
Vasco Matos's men currently sit fourth in the Primeira Liga standings with 18 points from the first 27 available, with only the 'big three' of Sporting Lisbon, Porto and Benfica picking up more points so far.
Nacional Primeira Liga form:
L
W
L
L
D
L
Nacional form (all competitions):
L
L
D
L
L
L
Santa Clara Primeira Liga form:
W
L
W
W
L
W
Santa Clara form (all competitions):
W
W
L
W
W
L
Team News
Having recently returned from the sidelines, Dudu made his first appearance since May as he was handed a 23-minute cameo in the cup against Sporting Lisbon last time out and the Brazilian forward could feature on Tuesday.
However, 20-year-old defender Chico Goncalves is out of contention for Nacional as he continues his long road to full fitness after suffering a severe injury back in August.
As for Santa Clara, Frederico Venancio missed the cup tie against Benfica after picking up a game-ending injury against Gil Vicente on October 25 and the 31-year-old is a major doubt for Tuesday's matchup.
Portuguese defender Pedro Pacheco has been out of action since picking up a severe knee injury in the Segunda Liga clash against Leiria in May and the 27-year-old star is also out of contention for the visitors.
Vinicius Lopes has been a standout performer for Santa Clara this season, and the former Botafogo forward, who has four goals and one assist in nine league games, should lead the attack, alongside Gabriel Silva and Joao Costa for the third consecutive game.
Nacional possible starting lineup:
Franca; Garcia, Ze Victor, Ulisses, Gomes; Esteves, Dias, Penha; Macedo, Isaac, Thomas
Santa Clara possible starting lineup:
Batista; Venancio, Rocha, Lima; Calila, Ferreira, Firmino, Nunes; Lopes, Costa, Silva
We say: Nacional 0-2 Santa Clara
Nacional and Santa Clara come into this one off the back of crashing out of the Taca da Liga and will be looking to secure a morale-boosting result. Matos's men have enjoyed the better of this fixture, given their solid form in the league, we fancy them to come away with all three points.