Background: HIV-infection may result in cognitive deficits, but the effects of pulmonary tuberculosis (TB+), a common co-morbid condition in HIV infection, on cognition in HIV infections are unknown . Accordingly, we examined the effects of TB+, on neurocognitive functioning in HIV-infected (HIV+) Zambian adults. Setting: All participants were drawn from HIV clinics in and around Lusaka, the capital of Zambia. Methods: Participants were 275 HIV+ volunteeers, of whom 237 were HIV+ and TB negative (HIV+/TB-), and 38 also had pulmonary TB+ (HIV+/TB+). Controls were 324 HIV and TB-uninfected (HIV-) healthy controls. All HIV+ were prescribed combination antiretroviral treatment (cART). Published, demographically corrected Zambian neuropsychological (NP) norms were used to correct for effects of age, education, sex and urban/rural residence. Results: NP deficits, assessed by global deficit scores (GDS), were more prevalent in this order: 14% (46 of 324) of HIV- controls, 34% (80 of 237) of HIV+/TB-, and 55% (21 of 38) of HIV+/TB+ group. Thus, both HIV-infected groups evidenced more impairment than HIV- controls, and the HIV+/TB+ group had a higher rate of cognitive impairment than the HIV+/TB- group. HIV+/TB+ patients were more likely to be male, younger, less educated, and have lower CD4 counts and detectable HIV RNA in blood compared to the HIV+/TB- patients. Conclusion: In HIV infection, TB may contribute to cognitive impairment, even after controlling for lower CD4 counts and viral load. Nevertheless, systemic inflammation from HIV and TB and more advanced immune deficiency at diagnosis of HIV, may contribute to impaired cognition in HIV+/TB+ patients.