Europa League holders Atletico Madrid face a mountainous task to stay in the competition after succumbing to a 2-0 defeat at the hands of Rubin Kazan at the Vicente Calderon.
Kurban Berdyev's men struck early through Gokdeniz Karadeniz in the first 10 minutes, and rode their luck for the majority of the match after the first half dismissal of captain, Roman Sharonov. However, the Russian side ultimately held out and netted again in the dying minutes through Pablo Orbaiz when Atletico were committing heavily for the equaliser.
The visitors outfit got off to the perfect start, netting the opening goal with just six minutes on the clock.
Karadeniz cut in from the left-hand side and slid the ball into the feet of Salomon Rondon, who drilled a shot towards the bottom corner. Sergio Asenjo in the Atletico goal managed to palm the ball to his right, but Kardeniz ran in to smash the rebound into the corner.
Los Colchoneros almost made an immediate reply. Arda Turan curled an outswinging corner kick to the edge of the area for Diego Godin, but the Uruguayan's impressive volley fizzed just past the left-hand post.
The first glimpse of Radamel Falcao came midway through the second half when the Colombian collected possession on the edge of the box and rifled a strike towards the bottom left corner, but his attempt crept past the post.
The prolific goalgetter was to be frustrated for much of the night, and neither goalkeeper was called into action on too many occasions until Rubin were dealt a blow just before the break.
Sharonov, who had previously been booked for a foul on Cristian Rodriguez, was shown a second yellow card when he upended Falcao as the Atletico man was jinking his way into the penalty area.
As the second half progressed Diego Simeone's side looked to utilise their man advantage, but the in-form Ryzhikov was proving to be a formidable barrier between the sticks.
In quick succession, the Rubin keeper denied Turan's strike from the edge of the box with an unconventional save with his legs, then managed to block a volley from Falcao from the same position.
And with 12 minutes remaining the Colombian turned swiftly on the edge of the box and powered a superb volley towards goal, only to see his attempt crash off the crossbar.
Rodriguez had a golden opportunity to snatch a leveller for his side in the last ten minutes, but sent his header wide of the mark despite having a large portion of the goal in which to aim.
Atletico continued to push further forward for an equaliser, but this proved to be their undoing. Goalkeeper Asenjo, in his attempts to find a goal from a corner kick, was caught out of position, and a pacey counterattack from the Russians saw Orbaiz run through and have the simplest of tasks to slot home into the empty net.
Rubin Kazan take a pivotal lead into the second leg in Russia, and Atletico's Europa League crown seems to be slipping from their grasp.