Rui Costa led the transfer activity as Benfica continued to invest heavily, spending nearly €19 million on Javier Balboa, Carlos Martins, Pablo Aimar and Sidnei and bringing in José Antonio Reyes and David Suazo on loan.

Benfica's season began inauspiciously, but they quickly recovered, gaining momentum domestically and eliminating Napoli to qualify for the group stage of the UEFA Cup.

Benfica tried to retake second place in the remaining eight matches, but in early May, the club dropped five points, sealing their fate; they finished third, missing the UEFA Champions League for a second consecutive season.

[4] With the unexpected resignation of head coach José Antonio Camacho on 10 March, assistant Fernando Chalana led the team through the final two months of the season.

[5] On 12 April Spanish manager Quique Sánchez Flores confirmed contacts from Benfica, who wanted him to take over the team immediately.

[6] Sánchez Flores declined the offer because he did not wish to be a temporary manager, and preferred to join a team at the beginning of the season.

[7] On 7 May, Vieira and Rui Costa travelled to Manchester to persuade Sven-Göran Eriksson to return for a third stint with Benfica.

[17][18] With Sánchez Flores in charge, Benfica added midfielder Hassan Yebda on a free transfer[19] and spent €4 million on Javier Balboa from Real Madrid.

[20] Balboa was signed only three days after the shock transfer of former Paris Saint-Germain loan Cristian Rodríguez to rival Porto.

[25][26] After a draw with Estori,[26] the club lost Guadiana Trophy matches to Blackburn Rovers and Sporting CP.

[27][28] That week Benfica made more squad adjustments, paying €5 million for 18-year old Sidnei[29] and releasing Petit after six years with the club.

[31] Before their presentation match with Feyenoord, Benfica signed Spanish winger José Antonio Reyes in a €2.6 million loan deal.

[35] Benfica's first competitive game was an away Primeira Liga opener against Rio Ave. Sánchez Flores did not have Reyes, and Jonathan Urretaviscaya started instead.

In the first leg of the qualifying stage for the UEFA Cup, the club faced Napoli at the Stadio San Paolo.

[46] The following Monday, Benfica visited the Estádio da Mata Real to play Paços de Ferreira in a 4–3 win.

[52] The victory placed Sánchez Flores in club history, since Benfica had never eliminated an Italian team after losing the first leg.

[56] To Sánchez Flores, the draw was due to Benfica's performance: low possession, missed passes and fouls resulting in free kicks.

Benfica met third-tier side Penafiel at home; unable to defeat them in regular and extra time, they required penalty kicks.

They took the lead with a 51st-minute goal from Ángel Di María, but Hertha responded with a 74th-minute equaliser when a shot by Marko Pantelić was deflected by Maxi Pereira.

After a first half in which they struggled to beat Estrela goalkeeper Nélson, in the 51st minute Nuno Gomes assisted Sidnei for the game's only goal.

[76] The result left Benfica on the brink of a UEFA Cup exit, and was a dark remembrance of their worst European defeat nine years before in Vigo.

In the 59th minute, David Suazo fired a powerful shot that beat Pedro Alves and put Benfica in the lead.

Benfica never overcame Nacional goalkeeper Rafael Bracalli, wasting an opportunity to open a four-point lead in the league table.

[91][92] The match ended in controversy after Cardozo had a goal disallowed because Miguel Vítor had deflected the ball with his hands.

At half-time, David Luiz headed in a controversial winner,[99] and Sánchez Flores said that the club were on course to regain their confidence after a poor past few weeks.

In the second half, Benfica held Porto until the 72nd minute, when Pedro Proença signalled a controversial penalty by Yebda on Lisandro López.

[115] Benfica's second league loss had troubling consequences; Sporting was tied for second place with 37 points, and Porto had a four-point lead.

[120] Miguel Vítor, who assisted the goal, told the media that Benfica wanted to keep winning in case Porto slipped.

[131] The race for second place (and a UEFA Champions League spot) also experienced a setback, since Sporting now had a four-point lead.

Note 2: Players with squad numbers marked ‡ joined the club during the 2008–09 season via transfer, with more details in the following section.