© 2020 Elsevier B.V.Objective: The aim of this study was to determine whether the progesterone-induced blocking factor (PIBF) level in women with unexplained infertility differed from that in fertile women. Study design: Volunteers between 18 and 35 years old were included in this cross-sectional study and were divided into two groups—the unexplained-infertility group and the control group. Demographic data on all the women were collected using a detailed questionnaire. The infertile participants and their male partners received complete infertility examinations according to the protocol. Blood samples were taken from all participants after the examinations during regular clinic visits. Serum PIBF levels were measured using an enzyme-linked immunosorbent assay. Results: Of the 46 healthy participants in the study, 22 had unexplained infertility. Age, body mass index, ethnicity, education level, age at first menarche, and length of menstrual cycles, serum follicle stimulating hormone, luteinizing hormone, estradiol, prolactin, thyroid stimulating hormone, and progesterone were similar between two groups. The mean right antral follicle count (AFC) was 6.6 ± 1.8 in the unexplained-infertility group and 6.5 ± 2.0 in the control group. The mean left AFC was 6.6 ± 2.0 in the unexplained-infertility group and 6.9 ± 1.5 in control group. The mean serum PIBF level was 6.92 ± 3.41 ng/mL in the unexplained-infertility group and 12.10 ± 10.47 ng/mL in the control group, which was a significant difference (p = 0.02). Conclusion: The present study showed that serum PIBF levels were significantly lower in unexplained-infertility group than in the fertile control group.