Fish-eye morphology is commonly observed in the very high cycle fatigue (VHCF) regime of additively manufactured Ti-6Al-4V alloys. However, its occurrence and implications have been less extensively studied in the high cycle fatigue (HCF) regime. In this paper, the fatigue performance and relationship between fish-eye morphology, fatigue life, and stress amplitude of selective laser melting (SLM) Ti-6Al-4V alloys were investigated in the HCF regime. Additionally, an in-depth analysis revealed that crack initiation in hot isostatic pressing (HIP) treated Ti-6Al-4V alloys predominantly occurs at facets, with a relationship identified between crack initiation sites and localized oxidation. Finally, based on the stress intensity factor (∆𝐾), a mechanistic model is proposed to explain the crack initiation and propagation behavior associated with fish-eye morphology in the HCF regime.