Background: It is vital to recognize the cause of an infection to enable earlier treatment. Studies have shown that procalcitonin (PCT) and C-reactive protein (CRP) have very high sensitivity and specificity for diagnosing serious bacterial infections (SBIs), with PCT performing better than CRP. Methods: Multiple databases were searched for relevant studies, and full-text articles involving diagnosis with PCT and CRP were reviewed. All meta-analyses were conducted with Review Manager 5.0. Sensitivity and bias analyses were performed to evaluate the quality of articles. In addition, a funnel plot and Egger test were used to assess possible publication bias. Result: A total of 17 articles met the criteria for inclusion. The concentrations of both PCT and CRP were higher in the SBI group than in the nonbacterial infection group. Sensitivity for differentiating bacterial infections from nonbacterial infections was higher for PCT compared with CRP, whereas there was no significant difference in specificity. The area under the summary receiver operating characteristic curve for PCT was larger than that for CRP. Conclusion: Both PCT and CRP are useful markers and should be used to evaluate SBIs with fever of unknown origin.