The Portuguese said there was a "clear campaign" against his Chelsea side to influence referees after Anthony Taylor adjudged Cesc Fabregas to have dived during the 1-1 Premier League draw at St Mary's.
Mourinho was aggrieved as replays showed Fabregas was upended in the penalty area by Matt Targett, but the Spain international was shown a yellow card for simulation.
The former Real Madrid coach also referred to an incident in Chelsea's first Premier League clash of the season at Burnley, when Diego Costa was also cautioned for simulation.
Mourinho was charged with misconduct by the FA on Thursday, but has not been punished for his comments before last month's clash at Stoke City in which he called for strong refereeing from Neil Swarbrick.
A statement on the FA's official website said: "Jose Mourinho has been charged by The FA for misconduct in relation to media comments he made following Chelsea's game against Southampton on 28 December 2014.
"It is alleged his remarks constitute improper conduct in that they allege and/or imply bias on the part of a referee or referees and/or bring the game into disrepute.
"He has until 6pm on 13 January 2015 to respond to the charge.
"The FA has also reviewed pre-match comments made by Mr Mourinho on December 19 2014 prior to Chelsea's game against Stoke City and, having sought his observations on this matter, decided not to bring a disciplinary charge and instead issued him with a formal warning.
"The FA prohibit participants from making any pre-match media comments including comments of a positive nature concerning the appointed match officials for a particular fixture.
"Whether the official is identifiable by name or by implication, these are deemed to amount to improper conduct in breach of FA Rule E3."
