Cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) infections typically follow a benign course in immunocompetent individuals. However, critically ill patients may develop profound immune dysregulation associated with sepsis, trauma, prolonged mechanical ventilation, or immunomodulatory therapy, which may predispose them to reactivation of latent viruses. A growing body of evidence suggests that CMV reactivation in immunocompetent, critically ill patients is associated with adverse clinical outcomes, including prolonged mechanical ventilation, longer ICU stay, and an increased risk of secondary infections. The clinical significance of herpesvirus reactivation in this population remains incompletely defined, and diagnosis may be challenging due to nonspecific clinical presentation and limited availability of molecular diagnostics. The aim of this study was to present a case series of CMV and HHV-6 reactivation in immunocompetent, critically ill patients and to discuss diagnostic and therapeutic challenges in the context of current literature. We describe three critically ill patients who developed herpesvirus reactivation during hospitalisation. One patient presented with clinically significant CMV reactivation suspected to contribute to gastrointestinal and pulmonary manifestations in the setting of rising CMV DNAemia. Another patient was diagnosed with CMV-associated immune thrombocytopaenia. A third patient developed rapidly progressive neurological deterioration with cerebrospinal fluid pleocytosis and HHV-6 DNA detected in cerebrospinal fluid, consistent with suspected HHV-6-associated encephalitis. Herpesvirus reactivation may be considered in critically ill patients with unexplained clinical deterioration despite the absence of classical immunosuppression.