[2] FC Barcelona talent scouts spotted him and, in 2004, he was signed for its youth teams from CD Tenerife, first being coached by Guillermo Hoyos, who played him as a midfielder.

On 8 November 2006, at the age of 18, he made his debut with the first team, against CF Badalona in a Copa del Rey round-of-32 match, coming on as a substitute for Javier Saviola in the 83rd minute of a 4–0 home win (6–1 on aggregate).

[5] Impressed at the player's performance for the reserves, first-team manager Pep Guardiola called Jeffrén for the 2008–09 pre-season, where he played all seven matches scoring twice, including once on 30 July against ACF Fiorentina in the 47th minute of a 3–1 victory.

[7] On 19 December 2009, Jeffrén replaced Thierry Henry late into the FIFA Club World Cup final against Estudiantes de La Plata.

[8] Two days later, he picked up a leg muscle injury that left him out for 4–5 weeks in a 1–1 friendly draw with Kazma SC in Kuwait, in commemoration of the Asian side's 45th anniversary.

[9] On 10 February 2010, Barcelona announced Jeffrén had signed a contract extension with the club, keeping him at the Camp Nou until 30 June 2012 with a buyout clause set at €10 million.

[26] He made his debut on 9 February at home against Elche CF, coming on at half time for Víctor Pérez: he crossed the ball for Humberto Osorio's 2–2 equaliser, but only a minute later left the pitch with a muscular injury after his team had already used all three substitutes.

[35] He left in late January 2019 for AEK Larnaca FC in the Cypriot First Division[36] and, one year later, switched to the Croatian First Football League with NK Slaven Belupo.

In 2011 he was selected by manager Luis Milla for the European Championships in Denmark, appearing in three games and scoring in the semi-final against Belarus (3–1 win)[41] as the national team won their third trophy in the category.

[42] Following his Spanish international youth spell, Jeffrén showed openness to represent Venezuela at senior level,[43] an option he himself had discarded in 2010 when he was consulted by a journalist of his native country.