On 21 October 2000, in a match remembered for his compatriot's treatment by Barça fans on his return to the Camp Nou in the colours of new team Real Madrid, he scored in a 2–0 El Clásico win.

[10][11][12] Also, during his six-year stint, he always finished as their top scorer, also ranking high in the global domestic charts, notably in the 2002–03 season as he scored a Primeira Liga and career-best 18 goals.

[13] In the following campaign, Simão scored Benfica's second goal in a 2–1 extra-time victory over FC Porto in the final of the Taça de Portugal,[14][15] ending the club's eight-year silverware drought.

The 2005 summer transfer window saw Simão targeted by Liverpool[19] in an offer worth approximately £12 million, though negotiations reportedly failed over Benfica's increase in asking price.

He played in eight of a possible ten matches in the tournament, including the 1–2 loss at Manchester United in the group stage, firing his team level shortly before the hour with a free kick after he himself had been fouled by Alan Smith;[21] in the knockout stages he helped stun title holders Liverpool, unleashing an unstoppable shot into the top left-hand corner of Pepe Reina's goal, as the Portuguese won 2–0 at Anfield and 3–0 overall.

[29] On 14 January 2010, Simão scored twice in a 5–1 home victory over Recreativo de Huelva that qualified to the quarter-finals of the Copa del Rey (5–4 on aggregate), including through an 83rd-minute free kick from 20 metres to decide the tie.

[32] He also captained the side more frequently due to the absence of Antonio López, most notably in the UEFA Super Cup's 2–0 defeat of Inter Milan, where he set up a goal for Sergio Agüero.

[39] He scored his first goal with his new club on 7 December, featuring as a second-half substitute for Rui Fonte and heading in from a corner kick in an eventual 2–2 home draw against Sevilla FC.

[47] On 3 November, immediately after replacing compatriot Silas, he scored a free kick to close a 1–1 draw at Delhi Dynamos FC;[48] four days later, from the penalty spot, he decided an away win at Atlético de Kolkata.

He played in three of his country's six matches, his most notable appearance coming against England in the quarter-finals: he came on as a second-half substitute and seized on Frank Lampard's wayward pass and crossed for Hélder Postiga, who headed in unmarked scoring the equalising goal in the late minutes of the game, bringing it to extra time and an eventual successful penalty shootout, where he converted his attempt.

[61] In March 2009, Simão took leave from Atlético to aid in the search for Diogo, the four-year-old son of his elder brother Serafim, who was reported missing when playing in the sea off Matosinhos.

[63] Simão launched an instructional DVD titled Como Se Faz um Campeão (How to Make a Champion),[64] and was the protagonist of a campaign for television channel Sport TV HD.