River Plate of Argentina crashed out of the Copa Libertadores after a shock 4-2 loss to Paraguayan club Nacional on Thursday in the tournament’s Group 3.
Fellow Argentine team Boca Juniors also suffered a surprise 1-0 away defeat against Deportivo Cuenca of Ecuador, but the six-time former champions should still qualify from Group 2.
River’s last group match is now meaningless, while Boca need just a point from their final group fixture next week to qualify.
River’s loss meant Peruvian club Universidad San Martin qualified alongside Nacional of Uruguay from Group 3.
Two teams qualify from each of the eight groups of four to play in the Copa Libertadores knock-out round.
Nine teams have now booked their places in the next round, with 12 matches next week to decide the seven clubs that will complete the lineup.
Two groups finished their fixtures this week, with Sao Paulo and Defensor Sporting progressing from Group 4, while Estudiantes qualified behind Cruzeiro in Group 5.
Two-time former champions River Plate needed to avoid defeat against already eliminated Nacional to keep their qualification hopes alive and the Paraguayan side were not expected to provide stiff competition after taking just one point from four previous group matches.
River took the lead through a Radomel Falcao penalty after 41 minutes, but Nacional leveled with a penalty of their own by Fabio Escobar in first-half stoppage-time.
River, four points behind second-placed Universidad San Martin in the table at the start of play, pushed forward looking for a win in the second half, but Diego Buonanotte was sent off after 58 minutes and gaps in their defense proved costly.
Substitute Jorge Nunez scored in the 65th minute and 78th minute, while Carlos Ruiz struck after 73 minutes to put Nacional three in front.
River striker Marcelo Gallardo scored from a free-kick in the 81st minute to cut the deficit.
Nacional of Uruguay host Nacional of Paraguay and Universidad travel to River in the final fixtures next Thursday to decide which club tops the group.
In Ecuador, Boca Juniors appeared to be cruising to a 0-0 draw and the point necessary to progress from Group 2 in top spot, but a goal by Edison Preciado in the 77th minute gave Deportivo Cuenca victory.
Boca lead the group with 12 points, Cuenca and Tachira are tied on nine, while Guarani of Paraguay are bottom with no points.