The Premier League said Britain's decision to leave the European Union will not harm the prestige of the world's most popular domestic football competition but experts warned of long-term damage to football's transfer system.
The free movement of players around Europe, a legacy of the seminal 1995 Bosman ruling, together with huge television revenues raked in by Premier League clubs have made England the destination of choice for many of Europe's top players.
Last season, according to Sky Sports, 432 players from EU countries were registered to play in the 20-team Premier League.
Although they will not be affected immediately, Britain's eventual exit could spell trouble.
The Premier League said it would not try to second guess all the implications of Brexit until the dust settled on a seismic day for Britain on which Prime Minister David Cameron announced he would be standing down.
"The Premier League is a hugely successful sporting competition that has strong domestic and global appeal," a spokesman said in a statement.
"This will continue to be the case regardless of the referendum result," he added.
"Clearly, we will continue to work with Government and other bodies whatever the outcome of any process."
Currently players from outside the EU have to meet certain requirements before being granted work permits such as having played 30 percent of games in the two years prior to moving.
The signing of young players could also be affected as FIFA's rule that players aged under 18 cannot be transferred across borders would be applied to Britain.
Presently, it is against EU rules to restrict the movement of people aged 16-18. Arsenal are one club to benefit from that exemption, signing Spaniard Cesc Fabregas from Barcelona when he was 16.
Premier League clubs could find themselves missing out to German, Spanish and Italian clubs in the hunt for young talent.
Arsenal keeper Petr Cech, a veteran of 12 years in the Premier League having also played for Chelsea, reacted angrily to the news on Twitter.
"It looks like the biggest decision in the history of this country was made based on fake campaign and lies," he said.
FA chairman Greg Dyke, however, said Brexit could actually help English players get more opportunities.
"One of my concerns in my period as chairman has been the decline in the opportunities for kids at the bigger clubs to get through and into the first team -- very few make it," he told Sky Sports.
"If anything happens that gives them better chances, then I welcome it."
Simon Boyes, a lecturer in sports law at Nottingham Trent University, said Brexit could mean clubs struggle to meet quotas for overseas players as EU players would be included.
"Sports regulators would no longer be prevented by EU law from discriminating against EU nationals by including them in quotas or limits on the number of 'foreign' players in a team or squad," Boyes said.
"Even were an EU national granted a work-permit in the UK, they might still be limited by restrictions on foreign players."