Background: Sepsis has heterogeneous etiologies. Although bacteria are the most common causative agents, viral and yeast forms of sepsis also occur. Procalcitonin (PCT) is widely used to monitor severe bacterial infections and may support the differential diagnosis of infection etiology. Methods: We evaluated the diagnostic value of PCT in viral sepsis using PCT levels at ICU admission and PCT kinetics during ICU treatment. Results: During the COVID-19 pandemic, 191 adult ICU patients with sepsis and a positive SARS-CoV-2 PCR test at hospital admission were included and classified into two groups according to the presence or absence of bacterial or yeast co-infection. PCT showed a distinct diagnostic pattern influenced by the presence of co-infection. PCT remained low in isolated viral sepsis, whereas elevated concentrations were associated with superimposed bacterial or yeast co-infection and worse clinical outcomes. Overall mortality was significantly lower in patients with isolated viral sepsis compared to those with co-infection (50 vs. 69%, p = 0.009). Conclusions: In viral sepsis, persistently low PCT concentrations argue against bacterial co-infection, whereas elevated or rising values should prompt increased diagnostic evaluation. Although PCT provides clinically relevant diagnostic information, it must be interpreted cautiously and in conjunction with clinical assessment and microbiological data. PCT should serve as an adjunctive, not a standalone, marker of infection etiology in sepsis.