BackgroundThe relationship between inflammatory response, fish consumption, and mortality risk in older individuals is unclear. We investigated whether C-reactive protein (CRP) levels ≥ 0.1 mg/dL, fish intake, and inflammatory responses are associated with all-cause mortality risk in older adults.MethodsThis prospective cohort study included older adults aged 85–89 years from the Kawasaki Aging and Wellbeing Project, who did not require daily care. Cohort was recruited from March 2017 to December 2018 (follow-up ended on December 31, 2021). Dietary assessment was conducted using the Brief Self-Administered Diet History Questionnaire. Multivariate Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality in the CRP ≥ 0.1 mg/dL group; the CRP < 0.1 mg/dL group was used for reference. Within CRP ≥ 0.1 and < 0.1 mg/dL groups, participants were categorized into tertiles of fish intake. HRs and 95% CIs for all-cause mortality in the other groups were estimated using the lower tertile group as a reference.ResultsThe study included 996 participants (mean [standard deviation] age, 86.5 [1.37] years; 497 [49.9%] women) with a median CRP level of 0.08 (interquartile range [IQR] = 0.04–0.16). There were 162 deaths during 4,161 person-years of observation; the multivariable-adjusted HR for all-cause mortality in the CRP ≥ 0.1 mg/dL group was 1.86 (95% CI, 1.32–2.62); P < 0.001. In 577 individuals with median (IQR) fish intake of 39.3 g/1000 kcal (23.6–57.6) and CRP level of < 0.1 mg/dL, the multivariable-adjusted HR for all-cause mortality in the higher tertile group of fish intake was 1.15 (0.67–1.97); P = 0.59, non-linear P = 0.84. In 419 individuals with median (IQR) fish intake of 40.7 g/1000 kcal (25.0–60.1) and CRP level of ≥ 0.1 mg/dL, the multivariate-adjusted HR for all-cause mortality in the higher tertile group of fish intake was 0.49 (0.26–0.92); P = 0.026, non-linear P = 0.38, P-value for interaction = 0.040.ConclusionsA negative association between fish intake and all-cause mortality was seen in older adults with elevated CRP levels, which is a mortality risk factor. While the results may be limited owing to stringent methods ensuring impartiality, they offer valuable insights for future research.Trial registrationUMIN000026053. Registered February 24, 2017.