Obstructive sleep apnoea (OSA) is associated with increased cardiovascular disease (CVD) risk. In the general population, CVD events peak at 9:00-10:00 AM, associated with diurnal changes in thrombotic potential. However in OSA, these CVD events occur frequently at night. Measuring thrombotic potential across the sleep-wake cycle may provide insight into the temporal association of OSA with CVD. This study aimed to determine diurnal changes in fibrin generation in OSA and whether treatment of OSA with continuous positive airway pressure (CPAP) alters fibrin generation across the sleep-wake cycle. In a randomised placebo-controlled crossover trial, patients with OSA were assigned to two months each of therapeutic CPAP and placebo. After each treatment period, fibrin generation was determined by overall haemostatic potential assay at seven time points over 24 hours (h). Twenty-eight patients (25 men, 3 women) with severe OSA (Apnoea Hypopnoea Index = 37.9 ± 23.9/h, Oxygen Desaturation Index 31.3 ± 22.4/h) completed the study. All parameters, except lag time to fibrin generation, showed significant diurnal changes, both on CPAP and placebo. Compared to 9:00 AM, fibrin generation parameters were significantly lower at midnight and 3:00 AM for overall coagulation potential (OCP), overall haemostasis potential (OHP), maximum optical density, and maximum slope (all p≤0.001). CPAP produced no change in fibrin generation parameters compared to placebo. In severe OSA patients, fibrin generation peaked at 6:00 AM and 9:00 AM rather than during the sleep period (midnight and 3:00 AM). These findings suggest a prothrombotic shift in the morning similar to individuals without OSA. There was no difference between CPAP and placebo on fibrin generation.