Background: Immunotherapies effect adaptive or innate immune responses. Programmed-death 1 (PD-1), a cell surface protein on activated T cells, which, when bound to its ligands PD-L1 and PD-L2, inhibits T-cell activation. Inhibition can be associated with complicating immune-related adverse events (IRAEs). Immune checkpoint inhibitors (ICIs) are FDA approved for advanced NSCLC. Study aims: (1) determine if the use of ICIs nivolumab (N) and pembrolizumab (P) is associated with development of autoimmune diabetes and thyroid disease and (2) determine the impact of (N) and (P) on pre-existing autoimmunity. Methods: Prospective, biological and clinical end-point-driven study in subjects with NSCLC considered for 1st or 2nd-line treatment with N or P. Subjects were assessed for thyroid stimulation hormone (TSH), hemoglobin A1c (HbA1c), thyroid peroxidase antibodies (TPO), glutamic acid decarboxylase (GAD) antibodies and islet cell antibodies (IC) at time of treatment start and wk 16 end point. Results: 29 subjects enrolled with base-line laboratory testing of which 14 subjects could be assessed at wk 16. At baseline, 1/14 subject had abnl TSH but at week 16 all subjects had a nl TSH (p 0.0687). Subjects had nl TPO at baseline and only 1/14 had an abnl TPO at 16 weeks (p 0.1634 ) but TSH remained nl. All 14 subjects had nl GAD and IC antibodies at baseline and at 16 wks; however, 2/14 of subjects had abnl IC antibodies at 16 wks but had nl HbA1c. 6/14 had nl HbA1c at baseline and 1/6 went on to develop pre-diabetes and 1/6 developed diabetes at the 16 wks. 5/14 subjects had pre-diabetes at baseline: 1/5 had nl HbA1c while 1/5 developed diabetes at 16 wks. 2 subjects developing diabetes had no positive GAD or IC antibodies. 3/14 had diabetes at study start with no worsening of the HbA1c or diabetes-related complications at wk 16. Conclusions: ICIs can cause IRAEs. Study result suggests that treatments with N and P can cause new onset of non-immune diabetes mellitus. Clinical awareness is important while managing NSCLC patients on ICIs. Patient should be screened for diabetes and thyroid disease prior to therapy and with repeat testing so as to avoid treatment complications. Longer follow-up and further study of ICI-mediated auto-immune endocrinopathies is needed.