Ronald Koeman says referee Michael Oliver made "strange" decisions in his side's 1-0 Premier League defeat to Leicester City on Sunday.
The league leaders moved seven points clear at the top thanks to a header by captain Wes Morgan, but were fortunate not to concede at least one penalty at King Power Stadium.
Danny Simpson appeared to block Sadio Mane's goal-bound shot with his arm and Robert Huth could also have conceded a penalty for handball when Charlie Austin's cross struck him.
Koeman said he does not believe referees are "against" Southampton, but described decisions made by Oliver as "very strange".
"I don't think that they are against Southampton, but it is very strange," said Koeman.
"We started the game badly and lost control, but after 20 minutes we were dominating. But for the third match in a row we don't get a 100 per cent penalty - Stoke City away, Liverpool at home, and today two penalties."
Koeman noted the penalties could have helped Southampton get a key result in their chase to qualify for Europe, but instead they remain in seventh place.
"The big one is when Sadio Mane's shot hits Danny Simpson and it is a red card and a penalty.
"If it is not a handball, it is a goal. I don't know what they are doing. This is a big match. It is about the Premier League title and our ambitions to play in Europe.
"The second one was when Robert Huth handled.
"I don't say they don't deserve the victory, that they don't fight and have amazing spirit, but if it is a penalty and a red card they don't win."
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