A sponsored walk from west Oxfordshire to the Kassam will take place before the U’s entertain Plymouth in League Two.
The 12th Man fund is a fan-led initiative to raise money to fund players.
It has previously helped bring in players such as Jamie Cook and West Ham loanee Rob Hall.
The idea began in the summer of 2009 and as of the end of last month had raised a total of £45,477 through a variety of means including selling wristbands and pin badges and hosting a six-a-side football tournament.
Next Saturday’s walk, dubbed ‘12 miles for the 12th Man’ is the first 12th Man event of the new season, with more promised. Walkers will start at the Evenlode pub, just off the A40 at Eynsham, at about 9.30am and will aim to reach the Kassam Stadium with enough time to grab a drink before the 3pm kick off.
Organiser Danny Johnston said: “The more fans that get involved in the walk the better. Please get in touch if you would like to walk, or sponsor a walker.
“All the money raised will help the U’s to target promotion.”
New club chairman Ian Lenagan said: “The 12th Man do such a lot to help the club and we are pleased to see them going the extra mile once again.
“We hope as many supporters as possible get involved and show their support.”
Club captain Jake Wright, whose move to Oxford United on a three-year deal in 2010 was helped by the 12th Man fund, said: “It’s another great effort from 12th man. They do so much for the club and we really appreciate the way they get behind the club.
“Hopefully we can give them a win to celebrate at the end of their 12-mile walk.”