Introduction: Gram-negative bacteria are the major cause of urinary tract infections (UTI) in children. There is limited data on UTI systemic response as measured using C-reactive protein (CRP). Here, we report the association of CRP and UTI among children attending the Bugando Medical Centre, Mwanza, Tanzania. Methods: A cross-sectional study was conducted between May and July 2017. Urine and blood were collected and processed within an hour of collection. Data were analyzed using STATA version 13. Results: Of 250 enrolled children, 76(30.4%) had significant bacteriuria with 56(22.4%, 95%CI; 11.5-33.3) having gram-negative bacteria infection. There was dual growth of gram-negative bacteria in 3 patients. Escherichia coli (32.2%, 19/59) was the most frequently pathogen detected. A total of 88/250(35.2%) children had positive CRP on qualitative assay. By multinomial logistic regression, positive CRP (RRR=4.02, 95%CI: 2.1-7.7, P<0.001) and age ≤ 2years (RRR=2.4, 95%CI: 1.23-4.73, P<0.01) significantly predicted the presence of significant bacteriuria due to gram-negative enteric bacteria. Conclusion: C-reactive protein was significantly positive among children with UTI due to gram-negative bacteria and those with fever. In children with age ≤ 2 years, positive CRP indicates UTI due to gram-negative enteric bacteria.