Background: In clinical practice alterations in CA-125 concentration within normal range in patients with ovarian cancer after first-line treatment are common. Even minor increase in CA-125 concentration is associated with patients' anxiety and difficult interpretation and counselling for clinicians. The aim of this study was to evaluate the significance of CA-125 fluctuations within reference level in patients who suffered from ovarian cancer with complete response after first-line treatment. Results: 168 patients with epithelial ovarian cancer, who achieved complete remission after first line treatment were enrolled in the study. CA-125 concentration assessment was carried out during follow up visits. The recurrence of the disease was diagnosed on the first appearance of symptoms: clinical, radiological or histopathological/cytological. PFS and 5-year survival rate was calculated with Kaplan-Meier plots. Statistical analysis was performed with SAS / STAT® 9.4 / 14.4, SAS Institute Inc., Cary, NC, USA, 2017. Median concentration of CA-125 after first-line therapy was 10 U/ml. Increasing CA-125 concentration by > 5 U/ml, 3 and 6 months after the treatment was associated with higher risk of relapse (HR = 7.6, p < 0.0001 and HR = 5.29, p < 0.0001 respectively). 5year survival rate was significantly lower in patients with increased CA-125 by 5 U/ml, 3 and 6 months after therapy (56.79% vs 0 and 50.62% vs 15.55%). Conclusions: Increased concentration of CA-125 by > 5 U/ml within normal range, 3 and 6 months after treatment was unfavorable prognostic factor in ovarian cancer patients with complete response to primary therapy.