The England quartet were not the only Reds who lost a midweek international at home. Jonny Evans played a full match for Northern Ireland as they were beaten 3-0 in Belfast by Norway.
Patrice Evra's national team France won on their travels, 2-1 away to neighbours Germany, although he was an unused substitute.
Nani had to settle for a draw as Portugal were held 0-0 in Poland, one of the host nations for Euro 2012. The United star was substituted eight minutes from time.
Meanwhile, Javier Hernandez made an unsuccessful trip to the United States, as his Mexico team lost 2-0 to Colombia in Miami.
Earlier on Wednesday evening, young Reds striker Will Keane came off the bench for England's Under-21s and helped the side to see out an impressive 4-0 win over Belgium in European Championship Group 8. His United team-mate Ben Amos wasn't named in the 18 on the night at Middlesbrough's Riverside Stadium.
Paul Pogba got on the scoresheet for France's Under-19s but his late header wasn't enough to prevent a 2-1 defeat to Spain. Frederic Veseli played the second half of Switzerland Under-21s' 2-1 loss to Austria with the winner coming in injury time. Michele Fornasier's Italy Under-19s drew 1-1 against Israel.