Immune-mediated diseases wherein immune complex-mediated injury is predominant; plasma exchange remains a therapeutic option for vasculitis. Hepatitis B virus-associated polyarteritis nodosa (HBV-PAN) wherein immunosuppressants can be contraindicated, plasma exchanges have a proven role when combined with antiviral therapy. Plasma exchange by hastening the clearance of immune complexes is beneficial in acute organ dysfunction. A 25-year-old male presented with complaints of generalized weakness, tingling numbness and weakness of extremities, joint pain, weight loss, and rashes over arms and legs for 2 months. Hepatitis B workup showed high viral loads of HBV (34 million IU/ml) and hepatitis e antigen positivity (1129.06 U/ml). Cardiac workup showed elevated cardiac enzymes and decreased ejection fraction (40%-45%). The finding of contrast-enhanced computed tomography (CECT) chest and abdomen with CT angiogram abdomen was steady with medium vessel vasculitis. A diagnosis of vasculitis with probable etiology of HBV-related PAN with mononeuritis multiplex and myocarditis was made. He was treated with steroids, tablet tenofovir, and 12 sessions of plasma exchanges. On average, 2078 ml of plasma was exchanged during each session with 4% albumin as a replacement fluid using central femoral line dialysis catheter as vascular access on automated cell separator Optia ®Spectra (Terumo BCT, Lakewood, Co). He was discharged with the resolution of symptoms, including myocarditis and increase in power strength and still in follow-up. The present index case indicates that antiviral combined with plasma exchange after short-term corticosteroids is an effective therapy for HBV-PAN. TPE can be used as adjuvant therapy along with antiviral therapy in a rare disease like HBV-related PAN.