Although atrial fibrillation (AF) is the most common type of cardiac arrhythmia, its etiology is unknown in nearly 10% of cases. Growing evidence suggests that inflammation plays a significant role in the onset and recurrence of AF. The role of inflammation in the pathogenesis of AF has important clinical implications of which many practitioners are unfamiliar. In this article, we describe a case of a 29-year-old male, who presents the emergency department with inflammation-induced AF, secondary to acute appendicitis. The latter condition was initially missed due to the unclear link between both presentations. By the time the AF was pharmacologically managed, the inflamed appendix perforated, resulting in unnecessary pain and suffering. After the perforated appendix was drained and removed surgically, the patient recovered well, and a follow up echocardiogram was normal. Here we give a brief overview of the pathophysiological perspective linking AF to inflammation and subsequent clinical considerations in patient management.