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Abstract Background Inflammatory markers, such as high sensitivity C-reactive protein (hs-CRP), and cognitive impairment (CI) are associated with mortality; CRP is related to the deterioration of CI. However, it is still unknown whether these two indices predict mortality independent of each other. Furthermore, their joint effect on all-cause mortality has not been well established, especially in oldest-old adults. Methods Based on data from the 2012 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we included 1447 oldest-old adults (mean age 84.7 years and 58.7% were female, weighted) with information on hs-CRP (stratified by a cutoff value of 3.0 mg/L) and cognition (quantified by Mini-Mental Status Examination (MMSE) scored according to the personal educational level) at baseline. Mortality was assessed in followed 2014 and 2017 waves. Cox proportional hazards regression models were used, with adjustment for hs-CRP and cognition (mutually controlled) and several traditional mortality risk factors. Results During a median follow-up period of 32.8 months (Q1-Q3, 9.7–59.0 months), 826 participants died. Hs-CRP [HR > 3.0 mg/L vs ≤ 3.0 mg/L: 1.64 (95% CI, 1.17, 2.30)] and cognition [HR CI vs normal: 2.30 (95% CI, 1.64, 3.21)] each was independent predictor of all-cause mortality, even after accounting for each other and other covariates. Monotonic and positive associations were observed in combined analyses, in which the highest mortality risk was obtained in elders with both high hs-CRP> 3.0 mg/L and CI [HR: 3.56 (95% CI, 2.35, 5.38)].The combined effects were stronger in male and younger oldest-old (aged 80–89 years). Conclusion High hs-CRP and CI, both individually and jointly, were associated with increased all-cause mortality risks in Chinese oldest-old. Intervention strategies for preventing inflammation and maintaining adequate cognitive function may be more important in male and younger oldest-old for reducing mortality risk.