The burden of HIV infection is still high globally. It is worse in the Sub-Saharan Africa, including Nigeria. The impact of the pandemic is devastating among children, especially those from the low income countries. There is paucity of knowledge on the effect of HIV infection on serum C-reactive protein and the benefit of the test with respect to patient evaluation and monitoring. If CRP is found useful, it can be a cheaper means of monitoring the progression of infection and response to treatment in HIV infected children. The aim of this study was to estimate the value of serum C reactive protein and evaluate its association with the severity of disease in HIV infected children aged 6 months to 12 years in children’s clinic at University of Uyo Teaching Hospital. HIV infected children attending the clinic were screened through history taking, physical examination and bedside/laboratory investigations. Participants meeting the inclusion criteria were recruited consecutively until the sample size was achieved. A proforma was used both as the screening tool and for documentation of data generated. Data was subsequently transferred into Microsoft excel spreadsheet and analyzed using SPSS version 20. Serum CRP was estimated using enzyme linked immunosorbent assay. Eighty-five respondents aged between 6 months to 12 years were recruited and matched age and sex with same number of apparently healthy looking HIV negative controls. A total of 92 (57.50%) males and 68 (48.50%) females participated in the study, giving a male to female ratio of 1.35:1. The mean age of the study participants was 8.50 ± 3.36 years, majority of them being within the ages of 5 to 12 years.