Background: The COVID-19 pandemic has resulted in a decline in mental health, due to the stress imposed by direct effects (e.g., loss of loved ones) and indirect mechanisms (e.g., reduced social support due to preventative distancing measures). These effects are likely most salient in individuals with chronic conditions, including multiple sclerosis (MS), who experience psychiatric symptoms at higher rates than the general public. Objectives: This investigation sought to examine the change in rates of clinically significant depression and anxiety pre/post-pandemic in persons with MS and reports of loneliness. Methods: Participants included 142 individuals with MS who had previously participated in research led by the senior author. Participants completed an online survey in Aug-Sept 2020 assessing factors related to their employment and medication use in light of the COVID-19 pandemic, in addition to a general COVID-19 impact survey, and inventories of depression, anxiety, and loneliness. Data previously collected included assessment of depression, anxiety, and social support. Results: Rates of clinically significant depression and anxiety across timepoints suggest an increase during the pandemic (i.e., depression: 18% at prior vs. 29% at present; anxiety: 31% vs. 47%). Chi-square analyses revealed that individuals with prior history of depression or anxiety were likely to continue experiencing these symptoms during the pandemic (?2=16.54, p<0.001, ? 2=24.303, p<0.001), but also that a significant proportion of the sample was experiencing new onset symptoms (54% & 33%). Compared to those with prior history of symptoms, individuals with new onset symptoms experienced a significant change in emotional loneliness, such that they differed from non-symptomatic individuals during the COVID-19 assessment (ps0.05). Both depression and anxiety classification groups (i.e., new/current symptoms, existing/current symptoms, no symptoms) differed on all subscales of COVID impact (ps range: <0.001-0.023), with the largest effects observed in those with new symptoms. Conclusions: Individuals with MS are experiencing higher rates of depression and anxiety during the COVID-19 pandemic, including new onset of symptoms that appear to be directly related to COVID-19. MS clinicians should seek to address COVID-related stressors and resulting loneliness, particularly in new onset cases, as a means to improve mental health during this time.