OBJECTIVE: Older persons with human immunodeficiency virus (HIV) (PWH) are particularly susceptible to life-space restrictions. The aims of this study included: 1) using global positioning system (GPS) derived indicators as an assessment of time spent at home among older adults with and without HIV; 2) using ecological momentary assessment (EMA) to examine real-time relationships between life-space, mood (happiness, sadness, anxious), fatigue, and pain; and 3) determining if number of daily social interactions moderated the effect of life-space on mood. METHODS: Eighty-eight older adults (PWH n = 54, HIV-negative n = 34) completed smartphone-based EMA surveys assessing mood, fatigue, pain, and social interactions four times per day for two weeks. Participants' smartphones were GPS enabled throughout the study. Mixed-effects regression models analyzed concurrent and lagged associations among life-space and behavioral indicators of health. RESULTS: PWH spent more of their time at home (79% versus 70%, z = -2.08; p = 0.04) and reported lower mean happiness (3.2 versus 3.7; z = 2.63; p = 0.007) compared to HIV-negative participants. Controlling for covariates, more daily social interactions were associated with higher ratings of real-time happiness (b = 0.12; t = 5.61; df = 1087.9; p< 0.001). Similar findings were seen in lagged analyses: prior day social interactions (b = 0.15; t = 7.3; df = 1024.9; p < 0.0001) and HIV status (b = -0.48; t = -2.56; df = 1026.8; p = 0.01) attenuated the effect of prior day time spent at home on happiness. CONCLUSION: Accounting for engagement in social interactions reduced the significant effect of time spent at home and lower happiness. Interventions targeting social isolation within the context of constricted life-space may be beneficial for increasing positive mood in older adults, and especially relevant to older PWH.