Background/Objectives: This exploratory comparative cross-sectional observational study investigated brain fog symptoms, cognitive function, sleep quality, quality of life, and selected serum biomarkers related to inflammation and neurocognitive function in newly diagnosed patients with celiac disease (ND-CeD), patients with CeD on a gluten-free diet (GFD-CeD), and controls. Methods: A total of 62 participants were included: ND-CeD patients (n = 18), GFD-CeD patients (n = 17), and healthy controls (n = 27) with no statistically significant differences in age or sex distribution across groups. Brain fog symptoms and severity, cognitive function, sleep quality, and quality of life were assessed using the Brain Fog Scale (BFS), Brain Fog Severity Score (BFSS), Montreal Cognitive Assessment (MoCA), Single-Item Sleep Quality Scale (SQS), and World Health Organization Quality of Life Questionnaire-Brief Form-TR (WHOQOL-BREF-TR), respectively. Serum BDNF, S100B, TLR4, IL-6, and nitric oxide (NO) levels were measured by ELISA. Results: ND-CeD patients had higher BFSs and BFSSs and lower MoCA, SQS, and WHOQOL-BREF-TR scores than healthy controls (p < 0.05). GFD-CeD patients showed numerically intermediate or more favorable scores than ND-CeD patients in several outcomes; however, most differences from controls were not statistically significant. Compared with ND-CeD patients, GFD-CeD patients had higher WHOQOL-BREF-TR General Health, Psychological Health, and Social Relationships scores (p < 0.05). In exploratory within-group analyses, after correction for multiple comparisons, higher BFS scores were associated with poorer psychological health and lower MoCA scores, and higher MoCA scores were associated with better psychological and physical health domains, particularly in the ND-CeD group. In the adjusted regression model, older age, income status, and newly diagnosed disease status were independently associated with MoCA scores. No statistically detectable between-group differences were observed in serum IL-6, NO, BDNF, S100B, or TLR4 levels. Conclusions: These preliminary findings suggest that brain fog symptoms, cognitive performance, sleep quality, and quality of life may deserve greater attention at diagnosis and during follow-up in celiac disease. Although GFD-CeD patients showed more favorable scores in some outcomes, these cross-sectional differences should not be interpreted as treatment-related improvement. Larger longitudinal studies with objective assessment of gluten-free diet adherence, disease activity, micronutrient status, sleep quality, and gut-brain axis-related biomarkers are needed to confirm these findings.
