Stewart Downing, Dimi Konstantopoulos, Andy Lonergan and John Obi Mikel are set to be free agents in the coming summer.
The quartet are all out of contract and Middlesbrough have not offered them new deals to stay on.
Mikel and Lonergan joined on short-term deals last season, but Downing and Konstantopoulos are both long-serving players.
Downing is a product of the Boro Academy and having made his debut as a 17-year-old in 2002, he went on to make his 400th Boro appearance during his second spell with the club when he captained the side at Swansea City last month.
A League Cup winner in 2004, Downing played a pivotal role in the club’s run to the UEFA Cup Final, represented England at the World Cup in 2006, and was a central figure in the promotion success of 2016.
Greek goalkeeper Dimi also played a major role in the most recent promotion campaign when he kept 22 league clean sheets, including nine in a row in a record-breaking spell.
Dimi made a total of 112 appearances for the club after joining in 2013 and became the oldest player to wear a Boro shirt in January when he played against Peterborough United in the Emirates FA Cup.
Mo Besic, Jordan Hugill and Rajiv van La Parra are the other players to depart after their loan deals came to an end.
Besic made 39 appearances while on loan from Everton last season, his second with Boro, and striker Hugill featured 41 times, scoring 7 goals, after joining his hometown club on loan from West Ham.
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