This paper investigates the fatigue behaviour of pseudo-ductile Quasi-Isotropic (QI) interlayer hybrids with un-notched and open-hole configurations. Two different types of QI pseudo-ductile hybrids were evaluated; HighC, with carbon to glass thickness ratio of 0.29, that is made of thin-ply M46JB-carbon/epoxy and thin-ply Xstrand-glass/epoxy prepregs, and LowC, with carbon to glass thickness ratio of 0.19, that is made of thin-ply T300-carbon/epoxy and standard-ply S-glass/epoxy prepregs. The hybrid configurations were loaded at 4 Hz in tension–tension fatigue without any initial damage and at different percentages of the pseudo-yield stress (σ_py) at which damage initiates. It was observed that there is no stiffness reduction, after 100,000 cycles, for a stress level of 80 % and 50 % of the σ_py for the un-notched and open-hole laminates, respectively. By increasing the stress level to 90 % and 70 % of the σ_py for the un-notched and open-hole laminates, respectively, there is a gradual stiffness reduction due to the appearance of matrix cracking and delamination in LowC, but no gradual reduction and no visible damage were observed for HighC. The final failure is more brittle and happens at a lower number of cycles for HighC compared with LowC. Different damage extents were observed for the investigated laminates before the final sudden failure due to variables such as the ply thickness, the cyclic energy release rate and the interfacial fracture toughness.