Disruption of the normal circadian rhythm is a problem in modern life. Shift workers, frequent time-zone travellers and patients with sleep disorders are all affected by different degrees of circadian disruption. Many people are also affected by social jet lag (misalignment between biological and social time). Circadian disruption can cause cardiac rhythm disturbances, including sinus node bradyarrhythmia and tachyarrhythmia, impaired heart rate variability, ventricular dysfunction with frequent ectopic beats and even sudden cardiac death. Day time sleep is the common way for such people to restore their sleep, but day time sleep cannot provide the same cardiovascular restorative effect as night time sleep. Excessive daytime sleepiness after night shift is a prodromal symptom of myocardial infarction. Currently, there is little understanding of how circadian disruption affects the heart rhythm and poor guidance for the affected population on how to lower any risk. In this study, the effect of circadian disruption on the pacemaker of the heart, the sinus node, was investigated. In the mouse, circadian disruption was caused using a chronic ‘’jet-lag” protocol. Mice were grouped-housed under a 0700 lights on (zeitgeber time, ZT, 0), 1900 lights off (ZT 12) cycle (Greenwich mean time, GMT, +0 h) for three days, moved to a 2300 lights on, 1100 lights off cycle (GMT+8 h) for another three days, and then moved back to the GMT+0 h time zone for another three days. These cycles were repeated for 30 days. The ECG was recorded in the anaesthetised mouse under 1.5% isoflurane at 1 L/min flow rate with respiratory rate 80-100 breath/min. Circadian disruption caused a significant prolongation of the RR interval (corresponding to a decrease in the heart rate) and impairment of heart rate variability. The ECG from the anesthetised mouse showed the occurrence of atrial bigeminy (a normal sinus beat followed by a premature atrial ectopic beat and then pause). The incidence and duration of atrial bigeminy progressively increased during the 30-day circadian disruption protocol: atrial bigeminy was observed in 1 out of 20 mice at Day 0 and 7 out of 20 mice at Day 30, and the duration of runs of atrial bigeminy increased from 2.7 s at Day 0 to 11.2 s at Day 30. Poincaré plots confirmed an increased occurrence of atrial ectopic beats at Day 30. At Day 30, the sinus node was dissected at one of four time points over 24 h and the beating rate was measured. Frequent bigeminy in sinus node beating rate and a dampened circadian rhythm in the beating rate over 24 h. This revealed a circadian rhythm in the intrinsic beating rate of the sinus node. The circadian rhythm in the beating rate was dampened and shifted in the circadian disrupted mice as compared to a control group. In the isolated denervated sinus node, atrial bigeminy was observed in the circadian disrupted group, but not in the control group. To understand the mechanisms underlying the disturbances in heart rhythm, at Day 30 the pacemaker current, If (funny current), was measured in isolated sinus node myocytes at 6 time points over 24 h. There was a circadian rhythm in If density, but the circadian rhythm in circadian disrupted mice was dampened and shifted as compared to the control group. The effect of If on pacemaking can be estimated by measuring the decrease in beating rate of the isolated sinus node on blocking If by 2 mM Cs+. The decrease in beating rate on blocking If shows a circadian rhythm consistent with the circadian rhythm in If. This circadian rhythm was also dampened and shifted in the circadian disrupted mice. In the circadian disrupted mice, the change in beating rate on blocking If showed a circadian rhythm with a peak at ZT 6 and a trough at ZT 18 compared to ZT 12 and ZT 0 in the control group. The ion channels, HCN1 and HCN4, are responsible for If. At Day 30, HCN1 and HCN4 mRNA were measured at 6 time points over 24 h; both showed a circadian rhythm and, once again, the circadian rhythm was dampened and shifted in the circadian disrupted group. We have previously shown that the circadian rhythm in HCN4 at least is driven by a local circadian clock in the sinus node (Wang et al., 2016). At Day 30, mRNA for two circadian clock genes, Bmal1 and Clock, were measured at the same time points and, as expected, both showed a circadian rhythm and, once again, the rhythms were drastically altered in the circadian disrupted mice. In summary, circadian disruption causes a disruption of the intrinsic circadian clock in the sinus node and we suggest that this is responsible for a disruption in the circadian rhythm in pacemaking ion channels. In turn, this may be responsible for an alteration in the circadian rhythm in heart rate and the occurrence of atrial bigeminy. Although not yet measured, it is possible that analogous changes are occurring throughout the heart and this may explain the occurrence of other cardiac arrhythmias with circadian disruption.