Lupus erythematosus (LE) is a multisystem inflammatory disease resulting from an altered T- and B-cell response. Among various pathogenic factors, viral infections have been implicated in LE exacerbation. We describe a patient with acute onset of subacute cutaneous lupus erythematosus (SCLE) and interstitial myositis with mitochondrial changes in the context of an associated hepatitis B infection and the response of myositis to antiviral treatment with lamivudine. Viral vectors may play an important role in LE. A hitherto undescribed myositis with mitochondrial changes was associated with hepatitis B infection and SCLE and improved with antiviral treatment.