While Watford currently sit in ninth place in the second tier, Southampton are third having compiled one of the longest ongoing unbeaten streaks in the top five divisions of English football.
Match preview
At a time when they have not lost a game since September 23, Russell Martin and his Southampton side would probably prefer to continue with their Championship schedule.
Last weekend, the Saints again impressed to record a 3-1 victory at Swansea City, that result proving important as Leicester City and Ipswich Town played out a 1-1 draw two days later.
Southampton are now within eight points of the leaders with 18 games remaining, momentum growing that they can eventually chase down a Leicester side that are beginning to show frailties.
Their away form has been an issue with just two wins being posted in six such fixtures in the Championship, yet consistently avoiding defeat on their travels means that it is a record that should be applauded.
Martin's side earned their place in the last 32 of this competition with a 4-0 victory over Walsall at St Mary's, the start of a three-game run where they have netted 11 goals.
Watford made more of a meal of coming through their tie against lower-level opposition, needing to overturn a deficit to beat National League side Chesterfield by a 2-1 scoreline.
That performance and near-miss had the potential to take the wind from Watford's sails, yet they have responded by collecting four points from their following two league games.
After recording a 2-1 triumph away at Queens Park Rangers, the Hornets travelled to Ashton Gate to face Bristol City and came away with a 1-1 draw.
Such a return has kept Valerien Ismael's side within five points of fifth-placed West Bromwich Albion, ensuring that a playoff bid remains very much alive heading into the second half of the season.
The corresponding league fixture took place as recently as December 9, Watford scoring a last-gasp equaliser to earn a 1-1 draw.
Watford FA Cup form:
W
Watford form (all competitions):
L
D
D
W
W
D
Southampton FA Cup form:
W
Southampton form (all competitions):
W
W
D
W
W
W
Team News
Ismael will likely make a number of changes to his Watford XI, including bringing back goalkeeper Daniel Bachmann between the sticks.
Jamal Lewis, Francisco Sierralta, Tom Ince, Matheus Martins and Vakoun Bayo can also expect to start at Vicarage Road.
While Emmanuel Dennis is available for selection after his return to Watford, he may be kept on the substitutes' bench.
Southampton will also rotate their squad for this contest with Jack Stephens, Shea Charles and Joe Rothwell all in line to be handed opportunities.
Carlos Alcaraz and Sekou Mara will also be considered for selection, but Che Adams's involvement may be dependent on whether a transfer elsewhere is in the offing ahead of the end of the January transfer window.
Watford possible starting lineup:
Bachmann; Andrews, Porteous, Hoedt, Lewis; Sierralta; Ince, Dele-Bashiru, Kone, Martins; Bayo
Southampton possible starting lineup:
Lumley; Walker-Peters, Stephens, Bednarek, Manning; Charles, Downes, Rothwell; A.Armstrong, Alcaraz, Fraser
We say: Watford 1-3 Southampton
With both teams expected to make changes, there is more of an unpredictability regarding the final outcome. Nevertheless, we cannot back against Southampton against any of the EFL clubs right now, even though they may have to showcase their superior class in the second half.