The striker signed a four-month contract with the Championship outfit in September after spending a month on trial at Deepdale.
However, a serious hamstring injury limited him to just two appearances in a North End shirt and the striker has now left the club after his short-term contract expired.
The 28-year-old played 25 minutes as a substitute against West Bromwich Albion in the Championship on September 18.
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Wickham then started the Carabao Cup tie with Cheltenham three days later but was injured early on during the fixture.
Wickham enjoyed a four campaign stint at the Stadium of Light – with loans at Leeds United and Sheffield Wednesday in between – following an £8m move from Ipswich Town back in 2011.
The fee broke Ipswich's record for transfer fees recouped and broke the transfer record for a Football League player moving to a Premier League club at the time.
And the deal was seen as a coup for the North East club to sign Wickham at the time, having beaten off interest from Liverpool to capture his signature.
The former England youth international found the net just 15 times in 91 appearances on Wearside before sealing a move to Palace on a five-year deal for an undisclosed fee in 2015.
Sources at the time reported the fee as a fee rising £9million, meaning around £17million in transfer fees has been spent on Wickham throughout his career.
Wickham scored two goals in 13 games on loan at Sheffield Wednesday in 2019-20 but did not feature at all last season as the Owls were relegated to League One.