Manager Mark Jones believes his players will go to Essex to take on the League Two club knowing that very few people will fancy their chances.
A look at the Vanarama National League South league table probably tells you why, Oxford are second bottom and haven’t won a league match since August 15.
But in the FA Cup it’s a different story altogether - so far they have beaten Whitehawk, Leiston and Bognor Regis.
This is the first time City have been in the first round since 2011 and have never reached the second round.
Jones says if they are to do that then they will be causing the upset of the weekend.
“We go to Colchester without any pressure on our shoulders and that could work in our favour,” said the manager, who last week said he is tired of hearing that his team are better than the league table suggests.
“We have maybe not been getting the rub of the green in the National League South but we have done well to still be in the FA Cup, no doubt about it.
“There is an opportunity to make a bit of history and although we know there is a huge task ahead of us we have got a chance.
“If we can go to Colchester, give a good account of ourselves and stay in the match for as long as possible then you never know what could happen.
“We’re excited about it. It’s a big ground, a Football League club and we’ve got nothing to lose.”