The visitors, meanwhile, will be hoping to turn the tide in the Brasileiro contest after losing five of their last six matches in all competitions.
Match preview
Santos know that if they are to climb up the Brasileiro table from 10th position then an upturn in fortunes is needed.
Their last 12 league matches have yielded only two victories, and they enter Wednesday's contest of the back of a 1-0 defeat to Avai.
Guilherme Bissoli's 10th-minute spot-kick proved enough to guide Avai to a victory that ended a four-game unbeaten away run in the Brasileiro.
Despite conceding at the weekend, Santos have been particularly strong defensively this season, with the hosts set to carry the third-best defensive record in the league into the midweek contest.
Although Santos have struggled to pick up wins of late, they can take confidence from the fact that they have won three of the last four meetings with Botafogo.
Meanwhile, Botafogo sit just one place behind Santos in the Brasileiro table, and a win on Tuesday would help them leapfrog their opponents.
However, if the visitors are to collect three points on Saturday then their needs to be an improvement in performance, with their last three games resulting in defeat.
The latest of those three defeats was a home encounter with reigning Brasileiro champions Atletico Mineiro, and although the hosts ran their opponents close, a second half strike from Matias Zaracho guided the visitors to a 1-0 victory.
Not only have they struggled to pick up points, but Botafogo are also finding it tough to find the net after failing to score in their previous three matches, while they have only grabbed one goal across their last six encounters.
While their eighth home league games have yielded seven points, Botafogo have fared much better on the road, with Wednesday's visitors boasting the joint-second best away record in the Brasileiro.
Santos Brasileiro form:
Santos form (all competitions):
Botafogo Brasileiro form:
Botafogo form (all competitions):
Team News
Santos are will be without Maicon and Lucas Pires, who are both sidelined with calf and knee problems respectively.
Rodrigo Fernandez, Sandry and Kevin Malthus are also expected to miss out for the hosts due to injury issues.
Meanwhile, Angelo Gabriel could return to the starting lineup after dropping down to the bench for the defeat to Avai at the weekend.
As for Botafogo, they also have a number of injury absentees, with Victor Cuesta and Patrick de Paula among those that are currently sidelined.
Diego Goncalves returned from injury to feature in the starting lineup at the weekend, and the 27-year-old is expected to retain his place in the side for Wednesday.
Erison will continue to lead the line for the visitors, with the forward looking to add to the six goals he has scored this season.
Santos possible starting lineup:
Paulo; Madson, Felipe, Bauermann, Jonatan; Zanocelo, Camacho; Gabriel, Baptistao, Braga; Leonardo
Botafogo possible starting lineup:
Borges; Saravia, Sampaio, Kanu, Hugo; Tche Tche, Oyama; Lopes, Fernandes, Goncalves; Erison