Functional analysis has shown that gain-of-function mutations (I57T and M23L) in the slow delayed rectifier potassium current (I_Ks), carried by the KCNE2 channel, are associated with early-onset lone atrial fibrillation (AF) (Nielsen et al., 2014). These mutations affect not only I_Ks but also the rapid delayed rectifier current (I_Kr) and the transient outward potassium current (I_to). Using biophysically detailed computer models, this study aimed to investigate the underlying mechanisms by which the two mutations (I57T and M23L) facilitate and promote AF. In the simulations, the MCZ (Colman et al., 2013) model of the human atrial cell was modified to incorporate experimental data on changes of I_Ks, I_Kr, and I_to induced by KCNE2 I57T and M23L mutations. The cell models were then incorporated into homogeneous multicellular one- (1D) and two-dimensional (2D) models of atrial tissue, as well as a 3D realistic model of the human atria. Functional effects of the two mutations on atrial electrical activities were quantified on the action potential (AP) profile and the AP duration (APD) restitution at the single-cell level; and on the conduction velocity (CV), the effective refractory period (ERP), and the wavelength (WL) restitutions at the tissue level. The widths of the temporal vulnerability window (VW) to re-entry were measured. Dynamical behaviours of re-entrant excitation waves (lifespan (LS), tip trajectory patterns, and dominant frequency (DF)) in 2D and 3D models were investigated. It was shown that both mutations shortened APD and flattened its restitution curve. At the 1D level, they abbreviated both ERP and WL restitutions and displaced the CV curve to the left, facilitating the conduction of atrial excitations at high rates. Although they reduced the temporal VW widths, KCNE2 I57T and M23L mutations increased the lifespan and stabilization of the re-entrant excitation waves at the 2D level, which was corroborated by 3D simulations. Collectively, these simulation results revealed the pro-arrhythmic effects of the KCNE2 I57T and M23L mutations, which are attributable to the shortened APD, ERP, and WL, and altered CV, which, in combination, facilitate the maintenance of re-entrant excitation waves leading to AF.