The Reds slipped to a shock 2-0 loss at the Riverside on Saturday afternoon and were overtaken in second spot by Chelsea who secured a last-gasp 2-1 Stamford Bridge win over Wigan.
The Red Devils are now seven points clear at the top of the table with a game in hand and Benitez concedes it is almost all over for his side.
Benitez said after the Boro defeat: “Before the game, it was very difficult – after the game, it is more difficult. It depends on United. It will be more difficult, clearly.”
On his side’s performance, the Spaniard added: “I don’t want to say too much, but for me, it is very clear. In the first 30 minutes, we had five chances and you have to take your chances.
“After the own goal, we still had chances. If you want to win, you have to score.”
A goal apiece from James Tomkins and Luka Milivojevic handed Crystal Palace a crucial 2-0 win over Huddersfield at the John Smith's Stadium on Saturday evening.
Manchester United bounced back from their Champions League exit as they beat Brighton 2-0 at Old Trafford on Saturday night to reach the FA Cup semi-finals.
Tottenham reached the FA Cup semi-finals after they cruised to a 3-0 victory over Swansea in their quarter-final clash at the Liberty Stadium on Saturday.
Premier League basement club West Brom squandered the lead as they suffered a 2-1 defeat to Bournemouth at the Vitality Stadium on Saturday.
Chesterfield boss Jack Lester felt his side were unlucky not to claim all three points after their 1-1 draw at Cheltenham.
New Swindon manager Phil Brown revelled in his side's victory at Cambridge in his first game in charge.