Background: Cutaneous warts are the commonest benign lesion produced by human papillomavirus. Lesions often regress spontaneously yet have a high rate of recurrence. They impair patients' quality of life and carry the potential risk of cancer. Nowadays, Candida antigen immunotherapy has become an encouraging therapeutic modality for warts. We tried to assess the role of the complement pathway and T helper 1 immune response in clinical response to Candida antigen immunotherapy via complement component 3c (C3c) and tumor necrosis factor (TNF)-α, respectively. Methods: A total of 44 patients with cutaneous warts were enrolled in the study. Patients were injected with Candida antigen at 2-week interval until complete clearance of the lesion or for a maximum of 5 sessions. Blood samples were collected before initiation and after completion of immunotherapy. C3 and C4 were measured using an automated turbidimetric method. Mannose-binding lectin (MBL), C3c, and TNF-α were measured using enzyme-linked immune sorbent assay. Results: A total of 56.4%, 17.9%, and 25.7% of the patients showed complete, partial, and no response to immunotherapy, respectively. Lesions on the dorsum of the foot and sole showed significant clearance (p value = 0.037). All patients had no deficient C3, C4, and MBL serum levels. C3c and TNF-α serum levels were significantly higher in non-responder group (p value < 0.001 and < 0.001, respectively). C3c and TNF-α serum levels were strongly correlated in all the studied patients (r = 0.8, p value < 0.001). Conclusions: Candida antigen immunotherapy is an effective therapeutic modality for cutaneous warts. C3c and TNF-α serum levels were higher in patients who failed to respond to immunotherapy.