Background— Electrical, structural, and Ca ²⁺ -handling remodeling contribute to the perpetuation/progression of atrial fibrillation (AF). Recent evidence has suggested a role for spontaneous sarcoplasmic reticulum Ca ²⁺ -release events in long-standing persistent AF, but the occurrence and mechanisms of sarcoplasmic reticulum Ca ²⁺ -release events in paroxysmal AF (pAF) are unknown. Method and Results— Right-atrial appendages from control sinus rhythm patients or patients with pAF (last episode a median of 10–20 days preoperatively) were analyzed with simultaneous measurements of [Ca ²⁺ ] _i (fluo-3-acetoxymethyl ester) and membrane currents/action potentials (patch-clamp) in isolated atrial cardiomyocytes, and Western blot. Action potential duration, L-type Ca ²⁺ current, and Na ⁺ /Ca ²⁺ -exchange current were unaltered in pAF, indicating the absence of AF-induced electrical remodeling. In contrast, there were increases in SR Ca ²⁺ leak and incidence of delayed after-depolarizations in pAF. Ca ²⁺ -transient amplitude and sarcoplasmic reticulum Ca ²⁺ load (caffeine-induced Ca ²⁺ -transient amplitude, integrated Na ⁺ /Ca ²⁺ -exchange current) were larger in pAF. Ca ²⁺ -transient decay was faster in pAF, but the decay of caffeine-induced Ca ²⁺ transients was unaltered, suggesting increased SERCA2a function. In agreement, phosphorylation (inactivation) of the SERCA2a-inhibitor protein phospholamban was increased in pAF. Ryanodine receptor fractional phosphorylation was unaltered in pAF, whereas ryanodine receptor expression and single-channel open probability were increased. A novel computational model of the human atrial cardiomyocyte indicated that both ryanodine receptor dysregulation and enhanced SERCA2a activity promote increased sarcoplasmic reticulum Ca ²⁺ leak and sarcoplasmic reticulum Ca ²⁺ -release events, causing delayed after-depolarizations/triggered activity in pAF. Conclusions— Increased diastolic sarcoplasmic reticulum Ca ²⁺ leak and related delayed after-depolarizations/triggered activity promote cellular arrhythmogenesis in pAF patients. Biochemical, functional, and modeling studies point to a combination of increased sarcoplasmic reticulum Ca ²⁺ load related to phospholamban hyperphosphorylation and ryanodine receptor dysregulation as underlying mechanisms.