In order to clarify the fatigue process for a micro-sized copper (Cu) single crystal with a double-slip orientation, a tension-compression cyclic loading test was carried out with in situ FE-SEM observation. Although the primary slip system B4 finally brought about a crack from eminent intrusions, the process was complex due to characteristic interactions among multiple slip systems. The process was approximately divided into three stages; early slipping, cave-in and damaging. In the early stage, two slip systems with high Schmid factor (SF), B4 and C1, worked at first, however both immediately stopped working. Extrusions/intrusions were caused by the survived slip system B5 (third-highest SF). In the second stage, a triangular depression was brought about by the cross-slip from B5 to C5 and localized wavy undulation was formed by the continuous cross slips. In the final stage, though both of B4 and B5 worked, the slip system with the highest SF, B4, dominated to form the eminent extrusions/intrusions, resulting in the fatigue cracking. The applied resolved shear stress amplitude was a few megapascals, indicating significantly lower fatigue strength than that of the bulk counterpart while it was in same range for that of micro-sized Cu with a single slip orientation. The complex fatigue damage morphology of the specimen was explained by accounting for the interaction of dislocations between the slip systems.