Large septic pulmonary embolus is a rare finding in right-sided endocarditis. The entity represents a challenging diagnosis due to its variable and nonspecific clinical and radiological presentation and similarities with other conditions. We present a case of a 41 year-old woman who developed a large main pulmonary artery embolus and bilateral cavitary lung nodules in the setting of severe sepsis. Pulmonary artery exploration and clot retrieval ultimately revealed a large septic embolus from Streptococcus mutans native pulmonary valve endocarditis. The diagnosis of septic pulmonary emboli from right-sided endocarditis should be considered in patients with ancillary findings of septic embolic phenomenon, particularly the presence of multifocal cavitary nodules and in the setting of appropriate predisposing factors.