The reigning world champion completed his unbeatable time of 1:21.865 on a five-lap run in the morning, seven tenths quicker than team-mate Mark WebberÃ¢â‚¬â„¢s time on Tuesday.
SÃƒÂ©bastien Buemi was closest to VettelÃ¢â‚¬â„¢s time for Red Bull junior team Toro Rosso, finishing half a second slower with some short afternoon runs as the Swiss driver completed 120 laps in the STR6.
Vitaly Petrov was third quickest for Renault, setting his best time of 1:22.670 in the morning session before switching to longer runs in the afternoon.
Just 11 cars were on track near Barcelona with Hispania Racing opting to wait until Friday to begin testing following the launch of their 2011 car, the F111, at the circuit.
McLaren experienced further problems with their MP4-26 which had been heavily criticised by Jenson Button earlier this week as an exhaust problem sidelined Lewis Hamilton before the 2008 world champion was able to get some competitive laps in.
The Woking-based team has much work to do to get the radical car up to speed for the first race in two weeksÃ¢â‚¬â„¢ time, and will return to the track on Friday for the final two days of the test.
Ferrari got their first run out of the final test with Felipe Massa behind the wheel of the 150 Italia as they tested new parts, including a new exhaust system.
The Brazilian finished fifth quickest with a time of 1:23.324 and looked consistent over longer runs, with no noticeable problems with the new additions.
Paul di Resta was again behind the wheel of Force IndiaÃ¢â‚¬â„¢s 2011 car, completing 118 laps on his way to sixth quickest with a time of 1:24.334 as he completed a full race weekend simulation with qualifying runs and live pit stops with full race crew ahead of his debut in Australia.
Kamui Kobayashi ran a similar programme to Sergio PÃƒÂ©rez on Tuesday as Sauber evaluated new parts on the C30 through various set-ups.
The afternoon saw the team gather data with Pirelli tyres in the to record a time of 1:24.436 for seventh quickest ahead of race simulations later in the week.
Mercedes also returned to the circuit with new parts, including a completely new rear as the team looks to resolve overheating problems. Nico Rosberg completed 100 laps as the team began with baseline runs, before moving on to set-up and tyre management in the afternoon with the GermanÃ¢â‚¬â„¢s quickest lapÃ¢â‚¬â€œfour seconds slower than VettelÃ¢â‚¬â„¢s timeÃ¢â‚¬â€œcoming on the first lap of a long run before a bodywork problem ended their session early.
Williams endured a difficult start to their test programme with a KERS problem halting Pastor Maldonado on track after just five laps preventing any further running until late afternoon as the team went through the lengthy process of removing it from the FW33. The Venezuelan was able to return to the track late in the afternoon to complete a further 24 laps of set-up work and aero mapping with a quickest time of 1:26.989.
Lotus had a productive day with Jarno Trulli completing 98 laps as the team worked on long runs to evaluate set-ups and tyre degradation, with a quickest time of 1:26.090 coming on towards the end of the afternoon to finish just two tenths slower than Rosberg.
JÃƒÂ©rÃƒÂ´me dÃ¢â‚¬â„¢Ambrosio was again bottom of the pile for Virgin Racing after completing 64 laps as the team evaluated the harder Pirelli compounds, despite an electrical problem which also caused damage to the gearbox.
The team also worked through suspension geometry changes ahead of the opening race. Despite only setting a time of 1:28.982, the team were happy with the outcome ahead of planned longer runs.
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BIOGRAPHY: Daniel Sturridge
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