Background: In refractory epilepsy patients with possible autoimmune-associated epilepsy (AAE) but negative antibody testing(-AB), immunotherapy trials (IMT) may still be pursued.The value of (IMT) in such patients remains unclear. For this reason, we reviewed their immunotherapy responses. Methods: Retrospective review of epilepsy patients admitted to the Epilepsy Unit between (2018-2021) who received (IMT). All had (-AB) and received immunotherapy (methylprednisolone (IVMP)-immune globulin (IVIg)-plasma exchange (PLEX)- rituximab).We considered responders when their seizure reduction was ≥ 50%. Results: 14 patients identified. Of them, 50%(n=7) females. Median age (43.5 year. IQR= 28.75-63.25). All refractory to ≥ 2 anti-seizure medications (ASM). Median epilepsy onset was (39.5 years. IQR=23.75-60.25).Median time from diagnosis until received immunotherapy was (15.5 months. IQR=12.75 -21.75). Patients received either IVIG+IVMP (35.7%, n=5) or IVIG alone (28.5%, n=4) or IVIG+IVMP+PLEX (21.4%, n=3) or IVMP alone (7.1%, n=1) or IVIG+IVMP+rituximab (7.1%, n=1). Median follow-up was 25 months.Although early immunotherapy responses were common, sustained response to immunotherapy at last follow-up was only in 21.4% (n=3). Factors confounding determination of immunotherapy efficacy were present in all responders (e.g:concurrent changes in ASM). Conclusions: Our findings suggest that (IMT) in patients with suspected (AAE) but with (-AB) are largely unsuccessful. This suggests an insufficient therapeutic effect after (IMT) or alternatively,non-immune-mediated mechanisms causing this type of epilepsy. Critical evaluations of (IMT)in such cases are needed.