Research applying fMRI to evaluate any activation in the central auditory nervous system (CANS) is currently limited, but has shown some promising potential. fMRI is likely to become the tool of choice for addressing many research questions concerning the auditory system, especially regarding the localization of the function of certain auditory areas and brain connectivity. The main aim was to determine the response of the central auditory nervous system (CANS) to sound in normal hearing adults with and without HIV/AIDS, using fMRI. A between-group comparative design was used to determine and compare the response of the CANS to auditory stimuli of a sample of 15 normal hearing participants without (HIV/AIDS) and 12 normal hearing participants with (HIV/AIDS). Structural and fMRI images were acquired using a 1.5T Siemens Magnetom Espree. Two different listening stimuli tasks namely nonsense syllables and warble tones were presented binaurally using earphones. These stimuli were presented with a block design with two conditions, silence (baseline) of twenty seconds and the stimuli task tone of twenty seconds. It was interleaved with duration of 20 seconds per block, with each block repeated four times. The task paradigm was done with blood oxygen level-dependent (BOLD) technique. Images were analysed by statistical parametric mapping software. A priori regions of interest (ROIs) for the CANS were defined and separate participant analyses were performed on the average signal in each ROI using the general linear model. The beta values generated from this analysis reflected the mean percentage signal change within the ROI of the CANS for the two tasks for each participant. A whole brain analysis was also done to determine and compare the multiple areas of activation and responses to the two tasks in the whole brain. Both groups of participants showed activation in all the ROIs of the CANS, but the mean percentage signal change in BA41 and BA42 differed significantly between the 2 groups with a p-value of 0.03 both BA41 and BA42. The control group showed a significantly greater increase in neuronal activity caused by cerebral blood flow to BA41 and BA42 than the HIV/AIDS group. The influence of possible confounding factors such as gender, age, and education on the mean percentage signal change in BA41 and BA42 in the two groups was also determined. Age (p = 0.95) and education (p = 0.68) had no statistically significant effect on the mean percentage signal change in BA41 and BA42 for any of the two groups in this study. However, gender had a significant effect for the mean percentage signal change for BA41 (p = 0.042) and BA42 (p = 0.037). The influence of the CD4 count and years on ART on the neural response of the ROIs CANS to the auditory stimulation (nonsense syllables) was also determined. The results showed a negative linear regression analysis, thus indicating an inverse correlation between the years on ART and the activated BOLD signals in BA41 and BA42 areas during the nonsense syllables task. The use of ART could have reduced the CD4 count in this study. Although this trend was observed, it would require a bigger sample to shed more light on these findings. Results of the response of the ROIs to warble tones indicated no significant differences between all the ROIs of the two groups, however a borderline significant difference (0.07) of activation occurred, namely the inferior colliculus in the right hemisphere of the HIV/AIDS group.