This is the first Champions League meeting between Barcelona and Manchester United since the final in 2011 in which Barcelona won, 3-1, at Wembley Stadium in London, England.
They also defeated Manchester United in the 2009 final at the Stadio Olimpico in Rome, Italy.
Manchester United's recent form has been poor, losing three of four in all competitions, while Barcelona are unbeaten in 16 straight.
Manchester United-Barcelona Betting Odds
Barcelona are currently even-money to win the opener at Old Trafford and -370 to progress over the course of two legs.
Manchester United are listed at +310 to advance to the semifinal and will need a strong result on home soil.
Barca are now the +300 favorites to win the Champions League following Manchester City's 1-0 loss to Tottenham in the quarterfinal opening leg Tuesday.
Injuries + Suspension News
Manchester United Injuries: F Marcus Rashford (probable), M Ander Herrera (questionable), D, Nemanja Matic (questionable), F/M Alexis Sanchez (doubtful),D Matteo Darmian (doubtful), M/D Antonio Valencia (out), D Eric Bailly (out)
Will Miss Second Leg if Booked:Herrera, Young, Matić, Shaw, Valencia
Barcelona Injuries: F Ousmane Dembélé (probable), Rafinha (out)
Will Miss Second Leg if Booked:Semedo
Betting Market Breakdown
All the line movement has been toward Barcelona since opening three weeks ago, though it's been a slower shift rather than a flood of bets.
Odds on Manchester United and the draw have both worsened, particularly based on their somewhat-poor form in all competitions.
They've lost multiple games to Wolves by the same 2-1 scoreline, once in the Premier League and the other in the FA Cup.
Three out of every four wagers has come in on Barca to pick up the victory so public bettors have definitely picked a side to win the first leg. They have not lost since a 2-0 defeat to Sevilla in the Copa del Rey quarterfinal back in January.
Leo Messi will hope to continue his rampant scoring pace against English opposition. He has amassed 22 goals in 30 Champions League matches and is listed at +110 to net one on Wednesday. That's certainly a tempting bet when looking at the Manchester United defensive backline.
In the totals market, sharp bettors have made their stand despite nearly 80% of tickets on the over. The vast majority of money has pounded the under (2.5), causing sportsbooks to adjust the juice considerably.
