Keith Curle said everybody at Northampton is "devastated" with the news defender Leon Barnett has been advised to retire because of a heart condition.
The 32-year-old centre-back has been told by medical professionals that it would be unsafe to continue training and playing.
Barnett had been having issues and was sent for further tests following a reaction in the match against Bury at the start of October.
Curle told the club website: "We are all devastated for Leon.
"The medical team made the correct decision to stop all activity, and after testing and second and third opinions, for his own health and safety, Leon has been advised to retire.
"It is very sad news. Leon is not just a good player, but an important figure off the pitch too.
"However, far more importantly for Leon and his family is that this has been diagnosed now and he is fit and well."
Barnett made over 350 appearances during his career and played in all four divisions of the English game for Luton, West Brom, Norwich, Wigan and Bury before joining the Cobblers.
Barnett played 24 times for Northampton before the game in October after signing on a free transfer in May 2017.