The Whites are a best-priced 31-20 for victory in Saturday's 3pm kick-off at Elland Road but the Saints are not far behind at 19-10 whilst the draw is on offer at 11-4.
Southampton's Adam Armstrong and United's record signing Rodrigo are both 15-2, followed by Whites star Raphinha and Saints forward Armando Broja who are both 38-5.
Chelsea loanee Broja netted the only goal of the game in the reverse fixture in October.
United youngster Sam Greenwood is next in the list at 42-5, followed by Southampton's Shane Long at 44-5 and then Whites winger Dan James at 9s.
Saints star James-Ward Prowse is then 10s, followed by team mates Theo Walcott (12s) and Mohamed Elyounoussi (25-2), United's Jack Harrison then next at 27-2.
In a very tight market, a 1-1 draw is favourite in the correct score market at 36-5 and Leeds are firmly expected to stay up in the longer term.
The Whites are currently fifth favourites to go down at 7-2, behind Norwich City (1-100), Watford (2-9), Burnley (4-7) and Everton (11-4).
Brentford are then 8s, followed by Newcastle United (33s), Brighton (150s) and Southampton (275s) who Leeds will hope are on the beach.