The two clubs have been vying for eighth and ninth positions in the table for most of the season, but could leapfrog Manchester United with a strong run-in.
With the Red Devils slipping up in recent weeks, the gap from them to the ninth-placed Saints, who are a point and a place below Newcastle, has reduced to only six points with seven games remaining.
The 52-year-old, who watched his side lose comprehensively at home to Everton on Tuesday at a local hotel, is still suspended from the touchline for a further four matches, though.
Tim Krul is not available for the Tyneside outfit, with the Dutch goalkeeper having been ruled out of their next "two or three games" because of a knee injury, so Rob Elliot will deputise in between the posts.
Davide Santon should shake off a nasty case of tonsillitis to return for the first time this month, having previously been sidelined by a knee problem, but his fellow full-back Mathieu Debuchy remains out.
Cisse has scored just two Premier League goals from open play in the last year, while De Jong has yet to net since joining on loan in January, but received a vote of confidence from Pardew this week.
The Japanese centre-back has suffered a knee injury, and Steven Davis may also miss the match on the South Coast after picking up a knock. Morgan Schneiderlin and Jay Rodriguez will need fitness tests, with Gaston Ramirez on standby to fill in if either is deemed unavailable to start.
Possible starting lineups
Southampton: Boruc; Chambers, Fonte, Lovren; Shaw; Cork, Ward-Prowse, Schneiderlin; Ramirez, Lallana, Lambert
Newcastle: Elliot; Santon, Williamson, Coloccini, Dummett; Sissoko, Tiote, Anita, Gouffran, De Jong, Cisse
Sports Mole says: 2-0