Adam Lallana looks set to follow Luke Shaw out of Saints, with a move to Liverpool understood to be close.
Teenage left-back Shaw completed his £25million-plus move to Manchester United this morning and he could swiftly be followed out of St Mary's by his former captain.
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Lallana is believed to be in Liverpool for a medical ahead of a move to the Reds, who earlier this month raided Saints for forward Rickie Lambert.
Brendan Rodgers' side saw several offers rejected for the England international this summer, but now appear to have struck a deal with Saints.
It is understood the deal could go through as early as Friday, with Lallana due to have a medical at Liverpool's Melwood training ground in the afternoon.
The move would end the midfielder's 14-year association with Southampton, who he joined from Bournemouth in September 2000 aged 12.
That deal included a 25 per cent sell-on clause, meaning the Cherries are set for a cash windfall from the reported £25million move.
The England midfielder was identified as Rodgers' primary target for the summer window and the club tried to get a deal done before the World Cup.
However, because of the turmoil at St Mary's after the departure of boss Mauricio Pochettino, the Saints were not prepared to let any players leave until they had appointed a replacement.
Lambert was allowed to move as Southampton classed that as a special case with the striker returning to his boyhood club.
With Ronald Koeman now in place at the south-coast club and Lallana returning home from the World Cup after England's disappointing tournament, things have progressed quickly.
Lallana will become Liverpool's third signing of the summer after Lambert and Bayer Leverkusen midfielder Emre Can, who will officially join the club on July 1.
Despite comments from Sevilla sporting director Monchi on Thursday suggesting a deal for left-back Alberto Moreno was dead, Liverpool still retain a hope of signing the defender as it is an area they desperately need to strengthen.
The two sides were "miles apart" in their valuations with the Spanish club holding out for £20million for the 21-year-old and Liverpool only willing to offer about £16million.
Moreno has distanced himself from a move but - with Rodgers needing reinforcements in order to be able to challenge both domestically and in the Champions League next season - there remains a chance the transfer could be revived.
"I never said that I wanted to leave the team," Moreno told Spanish newspaper ABC de Sevilla.
"I am happy here, Sevilla is the club of my life. There are many rumours but I only know that on July 7 I report back for training again.
"I am enjoying my holidays. We had a hard year and if I spent the summer thinking about these things (transfer speculation) then I can't rest.
"I am calm and my father and my agent will take care of my future."
Liverpool also retain an interest in Bayern Munich's Switzerland forward Xherdan Shaqiri, although the capture of Lallana may see Rodgers look elsewhere for other options.
With striker Luis Suarez facing a four-month ban after his biting incident at the World Cup, Rodgers could look at Lille's 19-year-old Belgium forward Divock Origi.
Lallana's exit is another blow for Saints, who was the last of three players included in England's World Cup squad remaining at the club.
Southampton have also this summer seen Pochettino depart for Tottenham, although the appointment of high-profile Koeman allayed concerns at St Mary's.
Furthermore, executive director Les Reed pledged before appointing the Dutchman that money from transfers would be ploughed back into the squad.
"We will only make decisions based on what's right and best for the club, so if we do sell players then it's guaranteed that any revenues we make will be reinvested in the team," he said.
"There's a logistical job to be done there because we do want to bring players in and improve the team so it's important that, whatever happens, when we do kick off on August 16 that we have improved the team and the depth and strength of the squad with the players that have come in, even if players may have gone out.
"However, our intention is to keep all of our core players - I wouldn't want people to think I've just opened the door for transfers, that's not the case."
It is fair to say, though, that Liverpool flexed their muscle by bringing Lambert and now Lallana to Anfield.
Reports suggest the Reds may not stop there with there, either, with Southampton's Croatia defender Dejan Lovren also reported to be on their radar