Southampton have requested referee Mike Dean does not officiate their upcoming fixtures and will appeal against the red card shown to defender Jan Bednarek in their 9-0 loss to Manchester United.
Saints also do not want Lee Mason, who was the fourth official at Old Trafford, to officiate their games.
Mason was the referee in Saints' controversial defeat by Aston Villa.
Fellow Premier League side Arsenal will appeal against defender David Luiz's dismissal in Tuesday's loss to Wolves.
Bednarek was the second player to be sent off for Ralph Hasenhuttl's side when he brought down Anthony Martial and conceded a penalty in the 86th minute.
Referee Dean initially only awarded a spot-kick to Manchester United but dismissed Bednarek after being instructed to watch replays of the incident on the pitchside monitor by video assistant referee (VAR) Graham Scott.
Poland centre-back Bednarek, 24, claimed that "Martial said it's not a foul" as he left the pitch, before the hosts went on to secure a record-equaling Premier League win.
Against Aston Villa on Saturday, Stuart Armstrong's effort struck Matty Cash on the arm, however VAR Dean did not instruct on-field referee Mason to award a penalty as he decided the ball had deflected off the defender's leg first.
Premier League clubs are unable to officially request that certain referees do not take charge of their games but it is understood that Professional Game Match Officials Limited will consider a number of factors when making match appointments.
