Background: Lithium compounds have been widely used in the treatment of manic-depressive illness. Several electrocardiogram (ECG) abnormalities, including ventricular arrhythmias, atrioventricular conduction abnormalities, T wave changes and QT interval prolongation, have been reported to be associated with lithium. However, the correlation between serum lithium levels and ECG changes has never been characterized in a systematic way. Methods: This retrospective study included 76 patients undergoing lithium treatment with available records of lithium levels. Eleven patients (4 men) had serum lithium levels >1.2 mEq/l and were diagnosed as lithium over range. Clinical characteristics and various ECG changes were analyzed in patients with and without lithium over range. Results: Patients with lithium over range had a slower heart rate and longer PR, QT and corrected QT (QTc) intervals. QTc interval >440 ms was more commonly found in patients with lithium over range (55 vs. 8%, p < 0.001). Similarly, diffuse T wave inversion was more commonly associated with lithium over range (73 vs. 17%, p < 0.001). The daily dosage of lithium was similar between patients with and without over-range lithium levels. When these two ECG changes were combined, the sensitivity and specificity in predicting lithium over range were 64 and 97%, respectively. These findings were independent of the concomitant use of β-blockers. Conclusions: QTc interval >440 ms and diffuse T wave inversion were significantly more common in patients with lithium over range, and were good predictors of lithium over range. More liberal checkup of the ECG in patients undergoing lithium treatment may be of help in the early detection of lithium over range.