The Catalan club travel to Stamford Bridge in midweek for the first leg of their last-four tie against the Premier League side.
However, they would be able to cut Madrid's domestic lead down to a point with victory at the Nou Camp on Saturday.
Despite the busy schedule, Mascherano believes that his team's focus should only be on their next match.
"The main thing right now is Wednesday's match. Afterwards, we'll think about the league and Real Madrid," the Argentine told reporters.
"We're in a Champions League semi-final and we have a great opportunity to reach the final. It would be a really big mistake to focus on Real Madrid first, because Wednesday's match is very difficult and will go a long way to deciding the tie.
"It'll be a really difficult tie that will depend a lot on getting a good result in the first leg against a team that has always been characterised by their tremendous physical strength, and which has some really experienced players."
Barca are bidding to become the first club to retain the Champions League trophy following its rebranding in 1992.