Intravenous immunoglobulin (IVIG) is a common treatment for the neurological autoimmune diseases multiple sclerosis, multifocal motor neuropathy, myasthenia gravis, and chronic inflammatory demyelinating polyneuropathy. However, there is scant literature regarding the psychological effects of this treatment on quality of life (QOL). Using illness intrusiveness theory and personal control theory, this correlational, cross-sectional study examined the relationship between the IVIG treatment experience and QOL in neurological autoimmune patients. Surveys were employed to collect data from 79 patients at a neurological infusion center in Phoenix, AZ. Quantitative analyses included correlation, multiple regression, and mediation analyses to determine whether (a) IVIG treatment experience predicted QOL measured by 10 Neuro-QOL scales, (b) illness intrusiveness mediated the relationship between IVIG treatment experience and QOL, and (c) personal control mediated the relationship between illness intrusiveness and QOL. IVIG treatment experience predicted QOL in 1 Neuro-QOL subscale; illness intrusiveness mediated 9 of the Neuro-QOL subscales using bias-corrected bootstrapping for statistical significance; and personal control did not mediate the relationship between illness intrusiveness and QOL. These results may affect social change by increasing the understanding of physicians, nurses, and patients regarding the psychosocial impact of IVIG treatment. Results from the study may provide insight for interventions to assist patients in adjusting to this form of treatment.