Background <p>Tuberculous meningitis (TBM) is a disease caused by <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) infection of the brain. Alkanes and other volatile organic compounds (VOCs) are biologically important metabolites that are used by infectious mycobacteria species for growth and survival strategies.</p> Objective <p>This study investigated the altered alkanes and other VOCs in the urine from paediatric cases with TBM.</p> Method <p>We used untargeted gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) to analyse and compare all volatile, underivatised compounds present in the urine from 27 confirmed cases of paediatric TBM over a treatment period of six months, as well as a control group (<i>n</i> = 13).</p> Result <p>Four elevated alkanes (pentadecane, 5,7-dimethyl-undecane, 4,7-dimethyl-undecane, and 2,6-dimethyl-undecane), three alkenes (decreased 2,5-dimethyl-2-hexene and 4,4-dimethyl-1-pentene, and increased 3-methoxy-1-pentene), and three other VOCs of biological interest (decreased 2-butenoic acid methyl ester and 3-heptanone, and increased 2-pyrrolidinone) were identified as statistically significant. These volatile compounds remained perturbed during the TBM treatment.</p> Conclusion <p>This study discovered new systemic metabolic information about <i>M. tb</i> in the host and the role of alkanes and VOCs in the potential persistence of <i>M. tb</i>. We demonstrate the value of targeting alkanes and other VOCs for future metabolomics studies of <i>M. tb</i>.</p>