BackgroundTuberculosis (TB) is treatable with a high cure rate. In South Africa, 70% of pulmonary TB is microbiologically confirmed. Autopsy studies of HIV-positive people found 45.7% undiagnosed TB cases.ObjectivesThe primary objective investigated whether CRP and a differentiated white cell count (WCC) and ratios thereof are useful screening tools for TB.MethodThis retrospective cross-sectional study included adult patients admitted to two tertiary hospitals in Bloemfontein with TB workups between April 2016 and September 2019. National Health Laboratory Service (NHLS) provided laboratory data. Tuberculosis Xpert®MTB/RIF, Xpert®MTB/RIF Ultra and TB culture were used as reference standard for TB diagnosis.ResultsThe study population comprised 1294 patients; 15.1% had TB, 56.0% were male and 63.1% HIV-positive. Patients with TB were younger (p< 0.0001; 95% CI: –8;–3 years). In the total population, WCC had the highest area under the curve (0.59). White cell count (p< 0.0001), neutrophils (p= 0.0003) and lymphocytes (p= 0.0394) were lower in TB patients, and CRP-WCC ratio (CWR) (p= 0.0009) and CRP-lymphocyte ratio (CLR) (p= 0.0386) higher. In HIV-positive patients, WCC (p= 0.0003), neutrophils (p= 0.002) and lymphocytes (p= 0.0491) were lower in TB patients and CWR (p= 0.0043) higher. No parameter reached the World Health Organization screening targets of 70% specificity with 90% sensitivity.ConclusionDifferentiated WCC and CRP are not useful in screening hospitalised patients for TB in our setting.ContributionOur study guides future research to augment current screening and diagnostic algorithms for TB, specifically in advanced HIV disease.