Currently, there is substantial ongoing discussion around the functional role of the thalamus in consciousness. What is missing in the literature, however, is a systematic investigation of the relevance of specific thalamic nuclei in pharmacologically and pathologically altered states of consciousness in humans. Using resting-state functional magnetic resonance imaging in both healthy anaesthetized volunteers (n = 16) and patients with disorders of consciousness (n = 22), we sought to identify which specific thalamic subregions in both cohorts may be differentially significant for loss of consciousness. Our findings revealed that, among all nuclei, the pulvinar was found to have the strongest functional connectivity change with loss of consciousness following anaesthesia, while demonstrating distinct functional connectivity patterns related to higher-order default mode and executive control networks. Remarkably, in loss of consciousness in disorders of consciousness patients, the ventral-latero-ventral was found to have the strongest connectivity change in comparison with healthy controls, while exhibiting discrete functional connectivity patterns related to higher-order default mode, executive control and frontoparietal networks. Furthermore, we provide evidence that this neural connectivity biomarker in patients also mirrored the changes observed at the behavioural level, which could have clinical implications for targeted deep brain stimulation in therapy for disorders of consciousness.