Background: Platelets have a vital role in antimicrobial host defenses. The objective of this study was to evaluate if increased mean platelet volume to platelet count (MPV/PC) ratio in acute ischemic stroke patients complicated with pneumonia was associated with increased mortality risk. Methods: The current study was conducted at Zagazig University Hospitals. It included 500 acute ischemic stroke patients classified as group 1 that included 51 patients complicated with pneumonia after admission and group 2 that included the remaining 449 patients. Clinical assessment was carried out to exclude comorbid medical illnesses likely to interfere with platelet function or morphology. Laboratory investigations including MPV/PC ratio and brain imaging were carried out for all patients. Results: There was a significant difference between both groups regarding age, National Institutes of Health Stroke Scale (NIHSS) score, and mortality within 30 days (p = 0.02, 0.03, 0.01). There was a significant difference between survivors and non-survivors of group 1 regarding to pneumonia severity index (PSI) classes IV and V (p = 0.01 and 0.02, respectively). Also, there was a significant difference regarding confusion, urea ≥ 7 mmol/L, respiratory rater ≥ 30 breaths/min, systolic blood pressure ≤ 90 mmHg or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 years at pneumonia occurrence (CURB-65) scores 3, 4, and 5 (p = 0.03, 0.02, and 0.01, respectively). Moreover, there was a significant difference regarding decreased GCS score at pneumonia occurrence, higher NIHSS scores, PSI, and higher MPV/PC ratio (p = 0.01, 0.01, 0.028, and 0.01, respectively). Age > 65 years, need for mechanical ventilation, GCS score of > 9, PSI class ≥ IV, CURB-65 scores ≥ 3, and increased MPV/PC ratio were all significantly associated with 30-day mortality in group 1 (p = 0.03, 0.01, 0.001, 0.04, 0.01, and 0.03, respectively). The predictors of 30-day mortality risk factors were GCS less than 9, increased MPV/PC ratio, and CURB-65 scores ≥ 3 (p = 0.001, 0.05, and 0.01, respectively). Conclusions: Once pneumonia develops, MPV/PC ratio could be considered a significant laboratory indicator of 30-day mortality.