Infusion reactions associated with Rituximab therapy have been reported including cardiac arrhythmia such as monomorphic ventricular tachycardia, supraventricular tachycardia, trigeminy, and irregular pulse [2,3,4]. Moreover, it can also cause bradycardia and AV blocks [2, 5, 6]. Based on our knowledge, this is the second case report of Rituximab causing high grade AV block as there has only been one case report of complete AV block after the fifth dose of Rituximab [5]. In the first reported case, the patient did not have underlying conduction system disease, but our patient did although they both received similar dose of Rituximab per cycle for the indication of DLBCL. In our case, it is likely that the underlying conduction system disease had put our patient into high grade AV block just after the first dose of Rituximab. The half-life elimination of Rituximab is proportional to dosage. After an initial dose of 375 mg/m2, the average half-life of Rituximab is 3.2 days (range, 1.3–6.4 days) [7]. For our patient, the AV block onset within 2 days of Rituximab infusion, and her conduction system failed to recover after more than 48 h of monitoring. There have been several explanations of the mechanism of Rituximab affecting the cardiac conduction system. Per Poterucha et.al., it was hypothesized that CD20 antigen may function as a calcium-ion channel. Rituximab can induce the death of CD20+ cells in many ways such as direct cytotoxicity mediated by antibody dependent cells and complement cascade as well as by indirect effects like apoptosis, structural changes and sensitization of malignant cells to chemotherapy [8]. Therefore, it is likely that Rituximab affects cardiac conduction system by inhibiting the calcium-ion-channel properties of the CD20 antigen on the cardiac myocytes. This mechanism appears to be the most plausible pathogenesis of our patient’s bradycardia: infusion initiation was associated with sinus bradycardia and worsening AV block which appears to be at the AV nodal level (improved conduction with exercise and narrow junctional escape with transient high grade AV block). A calcium channel blocking effect at both the sinus and atrioventricular node levels is a unifying explanation of those observations. Other hypotheses include elevated transforming growth factor-B promoting growth of reticulin fiber in cardiac myocytes which impairs contractility and conduction [9] as well as release of cytokines, such as interleukin-6 and tumor necrosis factor-alpha [5]. These cytokines can also mediate ventricular dysfunction, acute coronary syndrome, and myocarditis in addition to tachy-arrhythmias or brady-arrhythmias [10].