Carrie Carlisle tweeted to raise concerns for her husband's whereabouts.
She said: "#Missing Clarke's last known whereabouts was Manchester City Centre at 6am. If you see him please get in touch"
Carlisle, who has previously spoken of his mental health issues, was in a psychiatric unit for six weeks in 2015 after he was hit by a lorry.
Clarke Carlisle, 37, the former Leeds United player and chairman of the Professional Footballers’ Association, was once dubbed the nation’s most intelligent footballer.
In 2015, he launched a mental health charity called the Clarke Carlisle Foundation for Dual Diagnosis.
Anyone with information is asked to call police on 101