Leptospirosis and scrub typhus are common zoonoses and coinfection with both diseases has been reported sporadically, particularly in tropical and subtropical areas. A 53-year-old male presented with acute hypoxemic respiratory failure and septic shock due to leptospirosis and scrub typhus coinfection confirmed by serological assessments. Antibiotics, including intravenous penicillin and levofloxacin, were administered and human recombinant activated protein C was added because of a high risk of death due to septic shock with multiple organ failure. The patient's hemodynamics and hypoxemia substantially improved 4 days later and he had a complete recovery from the disease after 10 days of hospitalization. Coinfection of leptospirosis and scrub typhus may easily go unrecognized by physicians in febrile travelers or patients in the region where both diseases are endemic. In severe and critical cases of leptospirosis, scrub typhus, or coinfection with both, the use of APC in addition to appropriate antibiotic treatment and standard critical care might provide a greater chance for survival and a favorable outcome.