As well as their three-point cushion on second-placed Real Madrid, Barca also boast the better head-to-head record, which will be used to decide the eventual winner should the teams finish level on points.
It seems a healthy advantage with only six matches left, but Guardiola claims Barca cannot afford to drop any more points.
"I expected Madrid to win," he said, in reference to the capital club's 2-1 win at Almeria on Thursday night.
"I think they are going to win all of their games, so we have to go and win the championship ourselves. We won't give it away.
"They won't slip up because they are very good. They have lost just one game in the last 14 and their only objective during the week is to win the league game."
And the Barca coach is wary of a Madrid side renowned historically for their ability to grind out results.
"The three points and the 'goal average' (head-to-head) don't make me relaxed; maybe if it was another rival, but Real Madrid won't drop points," he said.