He spent the vast majority of his professional career in Spain, playing 280 competitive matches for six teams over 11 seasons – 179 in La Liga alone, being crowned champion with Valencia – but started and finished it at the same club, Peñarol.
For the 2006–07 campaign, after having spent one year in the sidelines, de los Santos joined Segunda División side Hércules CF. After two seasons where he was relatively used, he returned to Peñarol on 29 July 2008,[2] retiring from football two years later at the age of 34.