Objectives <p>This study assessed the nutritional and clinical status of Czech adolescents with anorexia nervosa (AN) during the SARS-CoV-2 pandemic (3/2020–3/2022), comparing them with those diagnosed before the pandemic (3/2018–3/2020) and healthy controls.</p> Methods <p>A single-center, retrospective, cross-sectional study involved AN patients diagnosed before (ANpreCov, <i>N</i> = 19) and during (ANCov, <i>N</i> = 18) the pandemic, along with a healthy control group (HC). Anthropometric, clinical, and laboratory parameters were compared across all groups.</p> Results <p>Despite a 64% increase in AN cases, no significant differences were found in clinical symptoms, laboratory results, diagnostic delays, hospitalization length, weight gain during hospitalization, or relapse and remission rates between the AN groups. Compared to healthy controls, AN patients had higher ferritin levels (<i>p</i> &lt; 0.01), higher ALT activity and vitamin B₁₂ levels (both <i>p</i> &lt; 0.05), and lower levels of non-esterified fatty acids (NEFA) (<i>p</i> &lt; 0.01).</p> Conclusion <p>Although AN cases significantly increased during the pandemic, the clinical and nutritional status upon admission remained similar before and during the pandemic. Elevated ALT, B₁₂ and ferritin are considered markers of malnutrition-induced liver injury. Reduced NEFA levels may result from increased oxidation or suppressed lipolysis, linked to alterations in the "adiponectin-GLUT4-AMP-activated protein kinase" signaling cascade.</p>