BACKGROUND The importance of the inflammatory processes and C-reactive protein (CRP) evaluation was observed. Only few studies used cut-off value <1 mg/L. We sought to evaluate the association between very low CRP (vlCRP) and health status, to describe the repetition of vlCRP and to identify predictors for repetition. METHODS A historical cohort study of all participants who underwent a routine annual check-up between January 2002 and July 2018 at the Tel Aviv Sourasky medical center. CRP test was evaluated in all participants. Individuals who use statins or with CRP >10 mg/L were excluded. CRP ≤0.12 mg/L was considered as vlCRP. RESULTS The final study cohort included 14,161 individuals. Of them, 5065 were females and mean age was 43.4 years (SD 10.6). vlCRP at first check-up was observed in 1299 (9.2%) of the participants. In multivariable analysis, older age, hyperlipidemia, hypertension and smoking were significantly associated with lower probability of vlCRP. At the second check-up, 50.1% vlCRP repetition was observed with no significant predictor from previous visit. CONCLUSIONS vlCRP is associated with younger age, non-smoking, and absence of hyperlipidemia and of hypertension. However, it may also be part of the individual physiology.