This study aimed to validate a high-sensitivity assay for C-reactive protein (CRP) in saliva as an alternative medium to study inflammation in large epidemiological cohorts and young people. We measured CRP in saliva and serum in 61 (29.5% males) healthy adult volunteers. We found a moderate-to-strong association between CRP measured in saliva and in serum (r=.72, p<.001). In agreement with the non-steroidal structure and the high molecular weight of CRP, we observed a low saliva-to-serum CRP ratio (1:1633.64). Furthermore, a dichotomous index of salivary CRP, equivalent to a clinically relevant serum CRP cut-off (3mg/l), was associated to known correlates of systemic inflammation (IL-6, BMI and smoking). Finally, we showed that CRP in saliva is stable at room temperature up to 8h after collection. Our study provides initial evidence suggesting that non-invasive assessment of CRP in saliva allows valid prediction of serum CRP. Salivary CRP may thus facilitate and promote research exploring the correlates of low-grade inflammation in epidemiological studies and makes it feasible to expand psychoneuroimmunology research to pediatric populations.