OBJECTIVES: This study aimed to explore time-varying associations between social engagement, living status and loneliness and neuro-immune markers in older adults, and whether results are explained by socioeconomic position, health behaviours or depression. METHODS: We analysed blood samples from 8,780 adults aged 50 and above from the English Longitudinal Study of Ageing across three waves of data collection: 2004/5, 2008/9 and 2012/2013. We used fixed effects modelling to estimate the relationship between loneliness, social isolation, living alone and levels of fibrinogen, insulin like growth factor-1 (IGF-1), white blood cell (WBC) count and C-reactive protein (CRP), whilst accounting for all time-invariant and identified time-varying confounders. RESULTS: Higher levels of social engagement and living with somebody were associated with lower levels of CRP, fibrinogen and WBC, while lower levels of loneliness were associated with higher levels of IGF-1. These associations were found to be independent of time-invariant factors such as gender, medical history, previous patterns of social behaviours, unobserved aspects of social class, and genetics, and time-varying factors such as income, physical health, health behaviours, and depression. CONCLUSIONS: Aspects of social engagement were associated with lower levels of inflammation whilst loneliness was inversely related to the regulation of inflammation. This suggests there could be different biological pathways involved in objective and subjective aspects of social connections.