People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.