This paper deals with the influence of buckles, a mesoscopic out-of-plane defect, on the fatigue behavior of a GFRP. Three cases were investigated: samples with no defect and two kinds of samples with buckle defects generated in the longitudinal or the transverse direction. Firstly, static tests were used to measure the differences in the mechanical properties of the two defect orientations and determine where the areas of maximum local strain were located. Secondly, fatigue tests were performed in the three configurations. The results revealed that both defect orientations have a significant effect on the fatigue behavior. The configuration with defects in the transverse direction was the most crippling condition but the longitudinal configuration was also strongly affected by the presence of mesoscopic defects. It was concluded that this mesoscopic out-of-plane defect has a major negative influence on the fatigue life of such a composite.