Sleep is fundamental for optimal psychomotor functioning, adequate immune responses, brain plasticity, memory, and ultimately our cognitive performance and well-being. Disturbed sleep is a common denominator of several neuropsychiatric disorders, including schizophrenia and major depression. More recently, it has also been linked to early cognitive decline and Alzheimer’s dementia (AD). Although the mechanisms underlying these associations are not clear, dysregulated immune system and microglia cells have been suggested to play a role. Microglia are the resident immune cells in the brain, which continuously survey the brain parenchyma through their branched projections to detect tissue damage or microbial insult. Via their cell receptors, such are as the Toll like receptors (TLR), they recognise important patterns and bind various compounds for elimination, including those whose accumulation may lead to Alzheimer’s dementia (e.g. beta amyloid). However, dysregulated microglia can also contribute to spread of toxic (pathological tau) proteins closely linked to dementia. Our group’s current and past work suggests that dysregulated sleep during obstructive sleep apnoea (OSA), one of the most common, and widely underdiagnosed sleep disorders, leads to aberrant brain immune responses (neuroinflammation) in patients. We and others have suggested that this could be in part due to activated microglia cells and maladaptive immune responses in the brains of patients with OSA. OSA is a debilitating chronic multisystem disorder, with ever-increasing prevalence, fuelled by an ageing population and the obesity epidemic. It is characterized by brief periods of repetitive upper airway occlusion, periods of low oxygen in the blood and dysregulated, fragmented sleep. Mechanisms behind OSA-induced brain injury in patients are still largely unknown. However, importantly, OSA is also known to be linked to early cognitive decline and AD, major depression, anxiety disorders, post-traumatic stress disorder, and even schizophrenia. Our preliminary data in animals further supports this hypothesis. More specifically, we have been able to show an increase in a specific TLR (TLR2) signal in a chronic intermittent hypoxia mouse model of OSA, suggesting adaptive activation of microglia in several regions of brain implicated in memory, mood and cognition. Other groups have described schizophrenia-like behaviours in mice lacking TLR2 receptors, further emphasising the importance of microglia in associated cognitive deficits in chronic neuropsychiatric disorders. In this study, we have studied mice with and without TLR2 receptors (e.g. transgenic TLR2-luc-& TLR2-KO mice) for shared neuroimmuno-cognitive mechanisms activated during fragmented sleep and episodes of low oxygen. All mice in our study underwent a protocol regime that closely mimicked the OSA disease process in patients, after which comparison of their behaviour and cognition was explored in detail. In addition, comparison of their structural brain grey and white matter changes, and intrinsic functional connectivity between the parts of the brain that deal with memory, emotions and cognition provides some further crucial insights into the shared immune adaptive and maladaptive responses at play.