Coma's error saw him lose 13 minutes four seconds and fellow KTM rider Despres now has an overall lead of 10:12 after the 270km trek from San Rafael to San Juan in Argentina.
Despres won the stage in a time of 3.48:38 which saw him finish 8:37 ahead of Dutchman Frans Verhoeven (Sherco) with Portuguese rider Paulo Goncalves (Husqvarna) third on the stage a further two seconds back.
Coma's time was only good enough to see him finish the stage in seventh.
"(The day) started quite badly for me because I smashed a finger this morning," Despres said. "My navigation repeater broke down after the first 100km.
"It was at least 300km long, but it was tough because the race director David Castera organised us a loop of 70km for just the bikes which was even tougher than endurance riding because the tracks were completely invisible because of the rain.
"At the river it was crazy, but I took my time and I didn't want to push too much. On the last bit on the special stage I was thinking that I wasn't sure if there was a bike in front of me. The track was not well marked, sometimes only a little bit, but apparently I've finished the special."
Coma said: "After 170km there was a different track for the bikes and the cars. I checked the road-book and thought I was on the right track, but then I saw that wasn't the case, because the next note was after 8km and it wasn't correct, so I turned round.
"Sixteen kilometres is a lot. So, after that, I went on the attack to try and gain back some time, but today was a difficult day, even if the scenery was spectacular.
"In the end, I've lost 13 minutes. It's a lot, but when you make a mistake, you shouldn't be surprised that the gaps open up. That's racing for you. Yesterday was my day, but today definitely wasn't."