Meanwhile, the away side travel to Rio Grande do Sul in search of a second consecutive victory after ending a two-game losing streak.
Match preview
Gremio would have aspired to build on their second-place finish in last year's Brasileiro Serie A - however, that has not been the case, as they have struggled to win games since the start of this campaign.
Renato Gaucho's side, who are yet to return to their original home stadium, Gremio Arena, due to flood damage in June, have only won three of their 13 league matches played, losing eight times and this has left them in 18th place with 11 points.
After a run of six consecutive defeats, Imortal Tricolor put together a three-match unbeaten run with two draws and a win, but they failed to extend this, losing 3-0 to Juventude on Sunday night.
Heading into their third league game in a week on Wednesday, Gremio risk going three matches without a win, having drawn with Palmeiras before Sunday's defeat.
With just one league win since the beginning of June, Imortal Tricolor are likely to be lacking in confidence, but Portaluppi's men will be encouraged by their results on home soil, where they have picked up 10 of their total points and have not lost in the last two matches.
Although their opponents are having a better season, the hosts will hope to extend their three-match unbeaten run in this fixture across all competitions, having won two and lost one.
Cruzeiro have their own struggles as well, and it has been about consistency since the season kicked off, experiencing periods without a win in the league.
Fernando Seabra's men went into their game against Corinthians on Sunday having lost two matches in a row - however, they were able to avoid a third consecutive defeat, comprehensively winning 3-0.
As a result, La Bestia Negra climbed to seventh place in the Brasileiro table with 23 points, four points behind fourth-placed Sao Paulo, having played one game fewer.
While boasting a perfect home record, Cruzeiro's issue has been their away form as they have only picked up four of their total points on the road, winning just once and losing five of eight away matches.
Currently on a run of five away matches without a win, losing the last three, Seabra's men have conceded 13 times on the road and scored just four goals - however, they will be hoping to secure a second away win given the state of their opposition.
Gremio Brasileiro form:
L
L
D
W
D
L
Cruzeiro Brasileiro form:
W
L
W
L
L
W
Team News
Gremio will be missing a number of players for this clash including former Chelsea striker Diego Costa, who is out until August with a muscle injury
Jhonata Robert is also ruled out with a knee and muscle injury, and Lucas Mila is facing an extended period on the sidelines due to an ACL injury.
Midfielder Andre Henrique and defender Fabio da Silva, are both sidelined with ankle and thigh injuries respectively.
Cruzeiro will also be without some players due to injury, including forward Juan Dinenno, who was signed earlier this year.
Arthur Viana is also out with a hip injury, while Rafa Silva is still recovering from a thigh injury which is expected to keep him out until for the next few weeks.
Gremio possible starting lineup:
Rafael; Pedro, Geromel, Martins; Reinaldo; Dodi, Villasanti, Ednilson; Gomes, Cristaldo, Pavon
Cruzeiro possible starting lineup:
Anderson; William, Villalba, Ze Ivaldo, Marlon; Pereira, Barreal, Silva, Romero; Robert, Veron