Due to current technological development, the fatigue life of several mechanical and structural components can exceed the high cycle fatigue barrier, conventionally established at 107 cycles. Given that, the evaluation for super long duration fatigue behavior has become extremely relevant for projects, where materials reach 107-1012 cycles during their life in service, creating the concept of very high cycle fatigue (VHCF). In particular, questions remain about the local influence of materials non-metallic inclusions on the mechanisms of crack initiation. This work aimed to analyze the influence of small defects in the fatigue life of the structural steel DIN 42CrMo4, under mega and giga regime cycles. In this regard, hourglass-shaped specimens were machined adopting holes with different diameters (0.3 mm, 0.4 mm, 0.5 mm and 0.7 mm) at its center region. These holes behaved as stress concentrations and were defined on the basis of Murakami’s theory, which proposes replacing the largest inclusion existing in the material’s region of analysis for a hole. Subsequently, the specimens were tested under ultrasonic fatigue with a frequency of 20 kHz and a loading ratio of -1. The adopted stress amplitudes were 310 MPa and 330 MPa, which represent values ranging from 34% to 37% of the analyzed materials fracture strength. Most of the experiment was consistent with respect to Murakami s prediction. The results revealed a direct relation between the defect’s size and the material s fatigue life, whereas with the increasing of the hole size, there was a reduction upon the material s fatigue life. All the holes, except for the 0.3 mm one, led to the specimens failure at a high cycle fatigue regime. Finally, fractographic analysis allowed to evaluate the fracture surface, indicating the hole as the cracks initiation site.