The result means the country set to host the Lions next summer will have no representatives in next week's semi-finals which feature the Stormers versus the Sharks in Cape Town and the Chiefs versus the Crusaders in Waikato.
The Reds trailed 20-10 at the break and were unable to work themselves back into the game in the final 40 minutes at the Suncorp Stadium.
With Quade Cooper having been banned for a week following a dangerous tackle in the final round of regular action and his replacement Ben Lucas succumbing to injury early on, the Reds struggled to get into their stride and were 20-3 down before Will Genia crossed for a converted try in the closing moments of the first period.
The Sharks remained in control for the rest of the encounter, with an injury-time try from Radike Samo coming way too late to be anything other than a consolation for the hosts.
"It's very disappointing to end the season on such a sad note but we tried our best and we can't complain," said Genia.
"It's quite tough when you have those injuries and we were very unlucky but, regardless of that, we didn't start well.
"We didn't give ourselves an opportunity to get into the game. We just released too much pressure when we were building.
"We're very disappointed with the result and I can't say anything else to be honest."