Platelets play an important role in hemostasis, inflammation, and immunity. Mean platelet volume (MPV), considered a marker of platelet function and activation, is associated with increased morbidity and mortality in sepsis, coronary artery disease, and chronic inflammatory disease. However, the clinical characteristics and prognostic significance of MPV changes for patients with pneumonia in the intensive care unit (ICU) have not been investigated. This retrospective study was conducted using data from an operational database of patients admitted to a medical ICU between October 2010 and October 2017. Of 235 adult patients with pneumonia admitted to the ICU, clinical characteristics and in-hospital mortality values were compared according to MPV, ΔMPVday1–2, ΔMPVday1–3, ΔMPVday1–4, and ΔMPVday1–Discharge between those who survived and those who did not. The MPV increased during the first four days for both non-survivors and survivors (P < 0.001). However, repeated measures analysis of variance revealed a significantly higher MPV rate over the first four days in non-survivors than in survivors. Additionally, the ΔMPVday1–2, ΔMPVday1–3, ΔMPVday1–4, and ΔMPVday1–Discharge values were significantly greater in non-survivors than in survivors. For in-hospital mortality, the optimal ΔMPV values were >0.9 fL, P = 0.020; >0.9 fL, P < 0.001; >0.8 fL, P < 0.001; and >1.3 fL, P < 0.001 on day 2, day 3, day 4, and at discharge, respectively. In conclusion, our findings demonstrate that ΔMPV during ICU admission may be used as a prognostic marker of mortality in ICU patients with pneumonia. Repeated MPV measurements throughout hospitalization may improve risk stratification for these patients, which could aid in improving patient outcomes.