Background Patients with influenza pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ARDS). Mean platelet volume (MPV), which reflects platelet size, is considered to be a crucial inflammatory marker. The study aim was to investigate the role of delta mean platelet volume (delta MPV) in predicting ARDS in patients with influenza pneumonia. Methods This retrospective study was conducted in a tertiary care centre in southern Thailand. Adult patients diagnosed with influenza pneumonia were enrolled from January 2015 to December 2020. Demographic data, laboratory investigations including delta MPV (MPV on day 2 minus MPV on day 1), management records, and clinical outcomes were collected for analysis. The study population was divided into two groups according to the development of ARDS. Results During the study, 1240 patients with laboratory-confirmed influenza were screened and 212 pneumonia patients were enrolled. Fifty-six patients (26.4%) met the diagnostic criteria for ARDS during hospitalization. Delta MPV was significantly higher in the ARDS group compared to that in the non-ARDS group (1.0 fL vs 0.2 fL, p < 0.001). Multivariable logistic regression revealed that delta MPV is an independent predictor of ARDS (OR 17.37; 95% CI 6.5–46.4; p < 0.001). Receiver operating characteristic curve analysis indicated a cut-off value of 0.7 fL for delta MPV (sensitivity 80.36%, specificity 80.77%) to predict ARDS in patients with influenza pneumonia. Conclusions Delta MPV strongly predicts ARDS in influenza pneumonia patients. Implementation of delta MPV may be useful in identifying at-risk patients who will require intensive care and ARDS prevention.