Even with the four-times World Player of the Year back in the starting line-up after injury, Barca struggled against an ultra-defensive Levante in Sunday's 1-1 La Liga draw and they had to come from a goal down to rescue a point.
Messi had one clear chance well saved by goalkeeper Keylor Navas shortly after halftime but otherwise made little impact against the massed ranks of the home defence and the Argentine is expecting a similar pattern to Wednesday's clash.
"We did everything possible to try to win but they play very deep and don't allow you space," he told reporters.
"It's a very tricky stadium to play at, but we tried our best," added the 26-year-old, who was out for two months after straining a thigh muscle in November.
"We played well enough to win but we were lacking a bit of good fortune. I expect Levante will use the same tactics in the Cup match."
If Barca, who have won Spain's domestic Cup a record 26 times, make it through to the last four after next week's second leg at the Nou Camp, they will play La Liga rivals Real Sociedad or third-tier Racing Santander for a place in April's final.
Santander, who are mired in financial difficulties and were relegated twice in the last two seasons, are the surprise packages of this year's competition and stunned top-flight sides Sevilla and Almeria on their run to the last eight.
They play at Sociedad's Anoeta stadium in San Sebastian on Wednesday (1900).
GRUELLING CALENDAR
On the other side of the draw, holders Atletico Madrid host Athletic Bilbao on Thursday (2000) and Real Madrid, who lost 2-1 to Atletico in last year's final, play at Espanyol on Tuesday
(2000).
Real look to be coming into form as the second half of the season gets underway and their 5-0 drubbing of bottom side Real Betis in La Liga on Saturday lifted them to within a point of joint leaders Barca and Atletico.
After Sunday's 1-1 draw at home to Sevilla, Atletico coach Diego Simeone dismissed a suggestion his players were feeling jaded due to the gruelling calendar and said the team needed to find ways of better dealing with defence-minded opponents.
"It makes it harder for us to generate goal-scoring opportunities and that's where we have to improve," the Argentine told a news conference.
"When we draw, and thank goodness we didn't lose, that doesn't mean that the team is tired," he added.
"We did not find a way to get through and that is to do with creativity in our play not fatigue.
"We need to take care of the details better because in the second half of the season teams don't try to play good football but are focused on accumulating points."
(Editing by John O'Brien)
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