The Argentinian has been missing with a thigh injury since November but is now back in training and took part in a full session alongside his team-mates on Monday morning.
Gerardo Martino may well choose to save the 26-year-old for Saturday's top-of-the-table clash with Atletico Madrid but, regardless of his exact return, the coach is excited to the have the four-time Ballon d'Or winner available.
"The best player in the world will have an impact on the team," he told www.barcelona.com. "We'll be even better."
If Martino decides that Wednesday is too early for Messi, then the manager still has a host of attacking options to choose from following the crushing 4-0 Primera Division win against Elche at the weekend.
Alexis Sanchez scored a hat-trick in that game with Pedro also netting his fifth goal in three matches and Neymar starting on the bench.
The last-16 action starts on Tuesday with defending champions Atletico taking on Valencia before the crucial league visit of Barca.
Diego Simeone's men are level with the Catalans at the top of the division meaning a league and cup double is a very real possibility.
But Simeone is refusing to get carried away and still believes that ending the dominance of city-rivals Real and Barca will be a huge ask for his team.
"It would be so much nicer to be in this position at the end of the season but there's a long journey ahead," he told www.clubatleticodemadrid.com.
"We must begin to look at Valencia with a new manager, it will be complicated. And then there's another big game at the Calderon next week.
"I am consistent with what I said. Look what it costs us to win a game. There is a huge difference between Real Madrid and Barcelona and for us it is the effort that we are trying to fight.
"But we cannot go further because they have more possibilities (in the squad)."
Juan Antonio Pizzi began his reign as Los Che boss with a 2-0 win over Levante at the weekend and will be looking to follow that up in the first leg at the Mestalla.
Wednesday night's action sees Segunda B side Racing Santander, the lowest-ranked team left in the competition, host Almeria while Segunda Division outfit Alcorcon are visited by Espanyol.
Real Betis take on Athletic Bilbao in Wednesday's other game whilst on Thursday, Real Sociedad host Villarreal, Levante travel to Rayo Vallecano and Osasuna are at the Santiago Bernabeu to take on last year's beaten finalists Real Madrid.