This study aims to use follicular fluid interleukin-6 (FF IL-6) levels as a biomarker for the prediction of intracytoplasmic sperm injection (ICSI) outcomes. A total of 82 couples receiving ICSI at the Assiut Centre for IVF and ICSI at El-Hyat Hospital, Assiut, Egypt, were included in this study between August 2021 and December 2022. The participants were between the ages of 20 and 40, with body mass index (BMI) ranging from 19 to 35 kg/m2. They received a typical antagonist regimen (Cetrorelix) and recombinant follicle-stimulating hormone (rFSH) until at least three follicles reached 18 mm. Ovum pick-up occurred approximately 36–37 hours after the introduction of human chorionic gonadotropin (HCG). Follicular fluid (FF) samples were collected, subjected to centrifugation, and stored for further analysis. The oocytes obtained were 12.67 ± 6.33 oocytes per patient, with a 78.12 ± 15.06% maturity rate. Pregnancy rate was 44%. FF IL-6 levels exhibiting a favourable correlation with the amount of blastocysts produced on the fifth day (r = 0.318, p = 0.013). FF IL-6 levels were significantly elevated in patients who successfully achieved pregnancy compared to those who did not (p < 0.00001). FF IL-6 levels affected the percentage of embryo fragmentation (p < 0.001) but not symmetry or cell number at the cleavage stage. The study suggests that FF IL-6 levels might be a potential biomarker for predicting ICSI success in patients with male factor and unexplained infertility. Higher levels of IL-6 are associated with increasing blastocyst formation, higher pregnancy rates, and less embryo fragmentation; however, more research will be needed.