This article reports on findings from a cross-sectional study (N = 378) of patients living with systemic lupus erythematosus (SLE).The purpose of this study was to identify and clarify the unique psychosocial challenges for those living with lupus. The specific analysis will help to develop a model to determine how different factors influence SLE patients’ psychosocial needs. Key findings indicate that the highest general causes of depressive and anxious feelings were changes in appearance due to SLE and limitations in physical abilities due to SLE. The more chronic the symptoms, the more likely it was that feelings of depression would ensue. The more education subjects had, the less likely they were to report feeling depressed or anxious about their SLE challenges. Those with no health care insurance reported the highest levels of depressive and anxious feelings, those with Medicaid reported the second highest, and those with Medicare reported the least SLE-related depression and anxiety. The great majority of SLE patients on medications experienced a wide range of side effects, the most prominent being hair loss. These findings can inform policy and programs as well as clinical initiatives for those affected by SLE.