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Objectives: The objective is to assess the interconnectedness of a network of health‐related quality of life (HRQoL) variables among people with HIV (PHIV) to identify key areas for which clinical interventions could improve HRQoL for this population. Methods: Between 2021 and 2023, we carried out a cross‐sectional study within the Spanish CoRIS cohort. We conducted a weighted and undirected network analysis, which examines complex patterns of relationships and interconnections between variables, to assess a network of eight HRQoL dimensions from the validated Clinic Screening Tool for HIV (CST‐HIV): anticipated stigma, psychological distress, sexuality, social support, material deprivation, sleep and fatigue, cognitive problems and physical symptoms. Results: A total of 347 participants, predominantly male (93.1%), currently working (79.0%), self‐reported homosexual (72.6%) and college‐educated (53.9%), were included in the study. Psychological distress showed the highest centrality in the network, indicating its strong connections with sleep and fatigue, cognitive problems and social support within the HRQoL network. Conclusions: Psychological distress, sleep and fatigue, cognitive issues and social support were identified as key factors in an HRQoL network, indicating that interventions focused on these areas could significantly enhance overall well‐being. [ABSTRACT FROM AUTHOR]