The static and fatigue bending behavior of wood-fiber-based tri-axial engineered sandwich composite panels (ESCP) has been investigated by four-point bending tests. Fatigue panels and weakened panels (wESCP) with an initial interface defect were manufactured for the fatigue tests. Stress σ vs. number of cycles curves (S-N) were recorded under the different stress levels. The primary failure mode in the fatigue tests was observed in the shear zone (epoxy debonding), which was different from face failure in the pure bending zone for the static bending test. For residual bending (RB) test, epoxy debonding failure occurred between the pure bending zone and shear zone. Macro cracks along the core/face interface developed as the number of cycles increased during the fatigue life. The crack propagation or damage for the panels submitted to fatigue test can be described as a three-stage damage process of first non-linear portion, followed by linear damage accumulation, and lastly nonlinear accelerated damage. Bending stiffness degradation at the higher load level had faster degradation during fatigue life. The dissipated energy of the panels was small due to the high stiffness of the materials.