Patients with ulcerative colitis in remission (UC-R) may experience symptoms consistent with irritable bowel syndrome (IBS). This prospective study aims to examine the relative influence of peripheral factors, such as gut mucosal inflammation, and central factors, like psychological conditions, on the severity of IBS symptoms to evaluates (1) the IBS Symptom Severity Score (IBS-SSS), (2) levels of inflammatory markers, and (3) the presence of psychological comorbidities across 3 groups: UC patients with IBS symptoms (UC-IBS), UC-R patients without IBS, and individuals with usual IBS. Rome III and IV IBS criteria were used in UC-R patients (Mayo score 0), with symptom severity measured by IBS-SSS. Serum and fecal inflammation markers were compared across UC-R without IBS, UC-IBS, and IBS groups. Among UC-R patients, 31.3% (26/83) met Rome III and 9.6% (8/83) met Rome IV IBS criteria. IBS-SSS scores were significantly lower in UC-IBS compared to IBS (n = 50; 167.5 [150-200] vs 255 [225-325]; P < 0.001). Fecal calprotectin levels were higher in UC-IBS than in UC-R or IBS (62.6 μg/g [34.1-85.6] vs 50.6 μg/g [27.3-96.6] vs 37.6 μg/g [12.1-62.3], P = 0.057), while other fecal markers (lactoferrin and MMP-9) showed no significant differences between UC-IBS and UC-R. Serum inflammatory marker including tumor necrosis factor-alpha, interleukin-6, interleukin-10, and granulocyte-macrophage colony-stimulating factor, C-reactive protein were similar across groups. Patients with IBS reported significantly higher anxiety, pain, functional impairment, and coping difficulties (all P < 0.001) compared to UC-IBS, with the lowest levels observed in UC-R without IBS. One-third and one-tenth of UC-R patients met Rome III and IV IBS criteria, respectively. UC-IBS had lower IBS-SSS and higher fecal calprotectin than IBS. Psychological comorbidities were worse in IBS, least in UC-R without IBS, suggesting more peripheral inflammation and less central involvement in UC-IBS.