Second seed Juan Carlos Ferrero has pulled out of the Pacific Life Open after coming down with chickenpox. Ferrero's withdrawal comes in the wake of those of David Nalbandian and Goran Ivanisevic on Thursday.
"Sometimes things happen and you can't do anything about it - I'm disappointed because I was looking forward to playing here," said Ferrero.
The 24-year-old will be replaced by Jeff Salzenstein in the men's draw which gets underway on Friday.
World number eight Nalbandian failed to recover from an ankle injury sustained in the Davis Cup in time for the first Masters Series event of the season, while Ivanisevic withdrew with a back injury and will be replaced by Antony Dupuis.
Switzerland's world number one Roger Federer is the top seed and the 32 seeds, including Britain's Tim Henman, all have byes into the second round.
Henman has what looks like a favourable draw, being in the same section as sixth seed Rainer Schuettler.
The draw has set up a potential third round clash between Andy Roddick and Marat Safin, who beat the American at this year's Australian Open.
The women's tournament, which begins on Wednesday, has been hit by several withdrawals including world number six Jennifer Capriati.