Exposure to ambient fine particulate matter (PM 2.5 ) was found to produce vascular injury, possibly by activating platelets within days after exposure. The aim of this study was to investigate the modulatory effects of dietary saturated fatty acids on platelet mitochondrial respiratory parameters following short-term inhalational exposure to PM 2.5 . A total of 22 healthy male volunteers were recruited from the Research Triangle area of North Carolina. Platelets were isolated from fresh whole blood samples and mitochondrial respiratory parameters were measured using an extracellular flux analyzer. Intake of saturated fat was averaged from multiple 24-hr dietary recalls. Daily ambient PM 2.5 concentrations were obtained from ambient air quality monitoring stations. Correlation and ANOVA were used in data analyses, along with the pick-a-point method and the Johnson-Neyman technique for probing moderation. After controlling for age and omega-3 index, the intake of dietary saturated fatty acids after reaching 9.3% or higher of the total caloric intake significantly moderated the associations between PM 2.5 exposure and several platelet mitochondrial respiratory parameters. In conclusion, dietary saturated fatty acids above 9.3% of total caloric intake influenced the relationship between short-term PM 2.5 exposure and platelet mitochondrial respiration. Further research is needed to understand these associations and their implications for cardiovascular health.