Real-time three-dimensional echocardiography(RT-3DE) has allowed a better assessment of LA volumes and function. We sought to assess the early change in left atrial size and function in patients treated with anthracyclines using RT-3DE. 61 patients aged 44.9 ± 11.9 years with large B-cell non-Hodgkin lymphoma treated with doxorubicin were studied. Blood collection and echocardiography were performed at baseline and 1 day after completion of the chemotherapy. Global longitudinal strain (GLS), maximum, minimum and pre-atrial contraction LA volumes were measured and reservoir, conduit and booster pump function were assessed. Despite normal LVEF, passive emptying percent of total emptying (0.51 ± 0.14 vs. 0.40 ± 0.12, P < 0.001) and passive emptying index (0.29 ± 0.10 vs. 0.23 ± 0.06, P < 0.001) were remarkably reduced compared to baseline values, while active emptying percent of total emptying (0.49 ± 0.14 vs. 0.60 ± 0.12, P < 0.001) and active emptying index (0.41 ± 0.16 vs. 0.47 ± 0.16, P = 0.048) were increased. GLS (-21.64 ± 2.83 vs. -17.30 ± 2.50) was markedly reduced, cTnT levels was elevated from 0.005 ± 0.004 to 0.020 ± 0.026 ng/mL at the completion of chemotherapy (P all < 0.001). Early LA functional change occur after doxorubicin exposure in patients with preserved LVEF, which could be detected by RT-3DE.