Introduction: Larger mean platelet volume (MPV), a measure of platelet activity, increases atherosclerotic cardiovascular disease (ASCVD) risk. Intake of n-3 polyunsaturated fatty acid (n-3 PUFA) found in fish may lower platelet count (PLC) and activity. We investigated the relationship between fish intake, PLC, MPV, and n-3 PUFA intake. Methods: We conducted a cross-sectional study among 9,870 participants (average age: 47.5 years; 55.9% men). N-3 PUFA intake was calculated based on fish intake frequency and information from the Nutritional Health Survey of Japan. Results: The average fish intake frequency was 2.14 ± 1.26 days/week. Higher fish intake frequency was associated with lower PLC and larger MPV. In a multi-regression analysis, fish intake frequency was a determinant of PLC (β = −0.081, p < 0.0001) but not MVP; however, lower PLC was a determinant of larger MPV (β = −0.421, p < 0.0001). N-3 PUFA intake significantly increased with increased fish intake frequency. Conclusion: Although higher fish intake frequency is associated with greater MPV, this relationship is not direct; instead, it may depend on lower PLC linked to higher fish intake. The antiplatelet effect of n-3 PUFA, which intensifies with higher fish intake, may suppress platelet activity with larger MPV, preventing ASCVD risk.

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