Ernesto Valverde's side are without a win in their last three games and last weekend lost at home to Espanyol, relinquishing their much cherished unbeaten record at their new stadium, San Mames Barria.
And against Betis, where they hope to reinvigorate their push for Champions League football, they will be without either of their top scorers, as Aritz Aduriz is suspended and Ibai Gomez has been ruled out of action for up to two months after tearing a hamstring.
In his pre-match press briefing, Valverde lamented the loss of Ibai, which he admitted had come at the worst possible time.
"It's a real shame because right in the middle of the situation we are in we have lost an important player who guarantees you goals," he said.
"During a season you expect to have problems like this, but they always come at a bad time. Given everything we are playing for now, it's an untimely loss."
The absences of Ibai, Aduriz plus Gaizka Toquero mean that Kike Sola is likely to start up front, with 20-year-old Guillermo Fernandez making the leap from the club's B team to the substitutes' bench.
Valverde also dismissed the suggestion that Betis, who have gained just 14 points all season, will be easy to beat.
"The history of Spanish football is littered with teams who everyone thought was headed for the drop and then stayed up," he said.
"Teams down to their last card often end up getting a lot of points and we think Betis could also do that. They are playing in a competition we would like to be in ourselves, the Europa League. They have a team that is good enough to be higher in the table but have gone on a negative spiral. But we have to go out to beat them because we need to win."
Betis produced a strong display in the first leg of their Europa League tie with Rubin Kazan on Thursday, but drew the game 1-1 after conceding a fiercely disputed penalty in the second half.
And Valverde is adamant that Betis' misfortune will not make things any easier for Athletic.
"If anyone thinks that we've got the game half won because they are bottom of the league, they are making a huge mistake," he added.
"Every team down near the bottom starts to pick up points, it's those teams that pick up the most points."