This paper aims to contribute in understanding the fatigue crack initiation mechanisms in metallic materials under high cycle multiaxial fatigue loadings. It addresses proportional and non-proportional multiaxial loading conditions with the analysis and observation of the cyclic plasticity development (mainly persistent slip band) until crack initiation (especially short cracks) on a pure oxygen-free high conductivity (OFHC) polycristalline copper. Observation and analysis techniques are based mainly on optical microscopy and scanning electron microscopy (SEM). It has been observed that the plastic slip multiplicity in grains seems more important for multiaxial loadings at a stress level corresponding to the same median fatigue strength at 106 cycles of the material.A multiaxial loading induces an additional multiplicity of the plastic slip in grains compared to uniaxial loading condition. For all the loading conditions investigated, although most of the grains exhibits single slip activated, analysis of the preferential crack initiation sites and modes show a higher probability of intragranular microcrack initiation in the multiple slip grains (with more than two slip systems activated). Most multiple slip grains and higher probability of crack initiation in these grains were observed especially for non-proportional multiaxial loadings. Finally, the effects of the biaxiality ratio and the phase shift on the fatigue crack initiation was highlighted.< Réduire