The present invention provides for methods of preventing and/or treating S. aureus-associated bacteremia and sepsis, and methods for preventing and/or treating S. aureus-associated pneumonia in immunocompromised patients using anti-S. aureus alpha-toxin (anti-AT) antibodies. Also provided are methods of reducing S. aureus bacterial load in the bloodstream or heart of a mammalian subject comprising administering to the subject an effective amount of an isolated anti-S. aureus alpha toxin (anti-AT) antibody or antigen-binding fragment thereof. Methods of reducing S. aureus bacterial agglutination and/or thromboembolic lesion formation in a mammalian subject comprising administering to the subject an effective amount of an isolated anti-S. aureus alpha toxin (anti-AT) antibody or antigen-binding fragment thereof, are also provided. Also provided are methods of preventing or reducing the severity of S. aureus associated pneumonia in an immunocompromised mammalian subject.