A 3-D computational fluid dynamics (CFD) model is presented to understand the influence of periodic operation in single phase packed bed reactors (PBRs). Unit cell approach is adopted to represent the packed bed with spherical particles having face centered cubic (FCC) and modified simple cubic (SC) packing arrangements. Three different on-off and min-max flow splits are analyzed and compared for single phase liquid flow operation. Comparison of results reveals the benefit of periodic mode in terms of homogeneous velocity distribution than that of the continuous mode operation. The effect is more pronounced at higher split ratios for FCC, and vice versa for modified SC arrangement. Moreover, on-off operation in both packing orientations exhibited a relatively better flow homogeneity as compared to min-max mode. Liquid distribution analysis indicates the improvement in flow homogeneity at the expense of a higher pressure drop in periodic operation. Single phase flow in packed beds finds several applications in heat transfer and reaction processes. This study essentially demonstrates the potential benefits of periodic operation to obtain homogeneous liquid distribution in packed beds with cubic close packing, which is of paramount importance in improving overall reactor performance.