To improve the efficiency of countercurrent chromatography (CCC) separations, we have previously proposed a new sample loading method called intermittent sample loading (ISL), in which continuous sample feed alternates with short periods of “clean” mobile phase feed to the CCC device. In semi-continuous separation processes, during sample feed periods, the sample is loaded in separate batches, each consisting of a series of intermittent sample loads. It was shown that the application of the intermittent sample loading method in the conventional isocratic CCC separations significantly increased process productivity and the concentration of compounds in the separated fractions. In this study, to further improve the CCC separations with intermittent sample loading, we discuss the application of the ISL method in the processes of close-loop recycling counter-current chromatography (CLR CCC). The advantage of the ISL CLR CCC over the ISL CCC is higher resolution and lower solvent consumption. Equations are presented that allow the simulation of periodic and semi-continuous ISL CLR CCC separations and the selection of optimal operational conditions for these separation processes. It is shown that the use of ISL technique in CLR CCC separations makes it possible to produce fractions of compounds with a much higher concentration than when using the conventional single sample loading method.