Primary infection by cytomegalovirus (CMV) commonly occurs subclinically or manifested by a self-limited mononucleosis-like syndrome in immunocompetent subjects. Severe clinical pictures are uncommon. We present a case of acute myopericarditis and hepatitis in a previously healthy 32-year-old man with primary CMV infection, assessed by serology and positive pp65 antigenemia. He was successfully treated with a course of oral valganciclovir therapy, with an immediate clinical response and normalization of laboratory tests. The literature on simultaneous presentation of CMV pericarditis and hepatitis in immunocompetent hosts, as well as the role of oral valganciclovir in this clinical setting, is reviewed.