INTRODUCTION: C-reactive protein (CRP) is a sensitive marker of systemic inflammation and is an independent risk factor for cardiovascular disease. The aim of the study was to examine the relationship between salivary CRP, cardio-respiratory fitness and body composition in a paediatric population. METHODS: This was a cross-sectional study of 170 black South African children (age 9.41 ± 1.55 years, 100 females, 70 males) in grades 3 to 7. Unstimulated whole saliva samples were obtained for the analysis of CRP. Height, mass, skin-fold thickness, resting blood pressure, and waist and hip circumference measurements were obtained. Cardio-respiratory fitness was assessed using a 20-m multi-stage shuttle run. Children were classified as overweight/obese according to the Center for Disease Control and Prevention (CDC) body mass index (BMI) percentile ranking, and meeting percentage body fat recommendations, if percentage body fat was ≤ 25% in boys and ≤ 32% in girls. The cut-off point for low cardio-respiratory fitness was a predicted aerobic capacity value ≤ the 50th percentile for the group. Contributions of low cardio-respiratory fitness, overweight/obesity, and not meeting percentage body fat recommendations, to elevated salivary CRP (≥ 75th percentile) concentration and secretion rate were examined using binary logistic regression analysis with a backward stepwise selection technique based on likelihood ratios. RESULTS: Poor cardio-respiratory fitness was independently associated with elevated salivary CRP concentration (OR 3.9, 95% CI: 1.7-8.9, p = 0.001). Poor cardio-respiratory fitness (OR 2.7, 95% CI: 1.2-6.1, p = 0.02) and overweight/obesity (BMI ≥ 85th percentile) (OR 2.5, 95% CI: 1.1-5.9, p = 0.03) were independent predictors of elevated salivary CRP secretion rate. CONCLUSION: The results suggest a strong association between poor cardio-respiratory fitness and/or overweight/obesity and inflammatory status in children, based on elevated salivary CRP levels.