The centre-back picked up an ankle injury in the 3-0 victory against Leicester two weeks ago, but it was not until this Thursday that manager Claude Puel confirmed the extent of the damage, with Van Dijk out for a minimum of two months.
The Frenchman will now have to work out how to use the limited resources available to put together a makeshift back-line that will be good enough to win at the home of football in three weeks' time.
A huge loss
Van Dijk's value to Southampton this season simply cannot be underestimated.
Until his injury, the Dutchman had player every minute of Southampton's Premier League campaign, besides the one game which he was suspended for; the trip to Everton, which the Saints subsequently lost 3-0.
The 25-year-old, who was recently appointed Southampton team captain following the departure of centre-back partner Jose Fonte, has unsurprisingly attracted the attention of the league's biggest and wealthiest clubs.
His aerial dominance, range of passing and raw athleticism mean he is ranked as one of the best centre-backs in the country.
A player of such ability is therefore worth his weight in gold to a club like Southampton, and they have relied on him heavily throughout the season, both as a defender and a leader.
Consequently, the fact that they will have to do without him for the majority of the rest of the season is a serious cause for concern on the South Coast.
Not many options
If losing Van Dijk on its own wasn't bad enough for Southampton, they now have to solve the issue of replacing him.
The glaring problem here is that Southampton, after inexcusably failing to purchase reinforcements in the January transfer window, have just three recognised centre-backs in their entire squad.
Admittedly, Maya Yoshida, who had spent much of the season on the bench, has performed exceptionally in recent weeks. With Fonte gone and Van Dijk in the treatment room, the Japan international is set to be the Saints' leader at the back.
However, Southampton's other two options; Jack Stephens and Florin Gardos, may not be up to the required quality.
Despite putting in the display of his short career in the EFL Cup semi-final second leg against Liverpool, 23-year-old Stephens has almost no Premier League experience and is yet to prove himself on a consistent basis. Gardos meanwhile, has started just one match in the last two seasons, that the 5-0 humiliation at the hands of Arsenal last Saturday.
Without Van Dijk, Southampton are lacking both quality and quantity in the defensive department, meaning the trio that are available will have to play out of their skin, and not get injured, for Southampton to have a chance at Wembley and finish the season successfully.
Puel refuses to be flustered
Despite the centre-back crisis, manager Puel has assured Saints fans that the absence of Van Dijk does not mean his side's chances of a major trophy are gone. While admitting that "it is not possible to replace a player like Virgil", he insisted that "we can give a good answer" without him.
Puel may turn to natural left-back Ryan Bertrand to fill in Van Dijk's position, but this reshuffle would only lead to Southampton being weakened in two positions rather than one. Nevertheless, Puel maintained that he can "compensate for his [Van Dijk's] quality".
After the failure to replace either Van Dijk or Fonte in the transfer window, the pressure is very much on Puel to prove that a new acquisition was not necessary.
However, there would be no better way to answer his critics than to win at Wembley.