BACKGROUND: Children with neuroinflammatory disorders have high rates of anxiety and depression, alongside low rates of physical activity. Given general concerns for mental and physical health in children during the COVID-19 pandemic lockdown, here we sought to understand how sleep, anxiety, depression, and physical activity changed with the lockdown in children with neuroinflammatory disorders. We hypothesized that outcomes would worsen during the lockdown, and that they would differ by underlying disorder category and age. METHODS: Patients attending a specialized neuroinflammatory clinic (n = 314) completed questionnaires (n = 821 responses; Jan 2017-Aug 2020) assessing sleep, anxiety, depression, and physical activity. Respondents had either: childhood-onset chronic or recurrent neuroinflammatory disorders (CRNI), a history of Autoimmune Encephalitis (AE) or Monophasic Acquired Demyelinating Syndromes (monoADS). We performed linear mixed models to examine the association between our outcome measures (sleep, anxiety, depression, and physical activity) and categories of disorder type, sex, age, physical activity, relapses, and time (pre- vs. post- COVID-19 lockdown). Participant ID acted as a random effect, to account for repeated measures. RESULTS: Sleep significantly increased in the first 6 months of the COVID-19 lockdown (F=56.85, P<0.001,). Across the whole group, anxiety and depression did not change with the pandemic, but we found differing trends by age category. Anxiety decreased in teenagers (≥13y) (Z = 3.96, P<0.001), but not for pre-teens. Depression remained higher in teenagers than preteens across both timepoints (F=6.30, p = 0.012). Physical activity levels did not change with the pandemic in comparison to pre-pandemic (F=1.92, P = 0.166). Anxiety was higher in inactive individuals regardless of timing (F=3.74, p = 0.024). CONCLUSION: For youth with neuroinflammatory disorders, the COVID-19 pandemic lockdown resulted in increased hours of nighttime sleep but did not result in significant overall changes in self-reported anxiety or depression. Pre-lockdown, teenagers had higher depression and anxiety scores than preteens. Post-lockdown, anxiety and depression scores decreased in teenagers compared to pre-teens. Physical activity was low both pre- and post-lockdown, and rates of anxiety were higher for inactive participants at both timepoints. Differences based on age suggest that younger children (<13 years) were more negatively affected by the pandemic than older children (≥ 13 years).