Fecal calprotectin (FC) is a well-integrated parameter in the monitoring of adolescent patients with inflammatory bowel disease (IBD). However, measurement of FC is limited by day-to-day-variation and by the feces consistency. Furthermore, adolescents are often noncompliant to deliver fecal sampling leading to suboptimal monitoring. Consequently, we see the need of a substitute biomarker whenever measurement of FC fails and aimed to investigate serum calprotectin (SC) in adolescents with IBD. In cross sectional data from 19 ulcerative colitis (UC) patients <18 years old, a Spearman correlation was used to analyze the correlation between SC, FC, C-reactive protein (CRP) and endoscopic and symptom scores. In longitudinal data collected from 20 UC and Crohn disease (CD) patients (10-17 years old), Mixed Effect Models (MEM) were used to analyze the association between SC, FC, CRP, and symptom scores. We found positive correlations between SC (19 samples) and the endoscopic score, symptom score, and CRP (r = 0.56, P = 0.01; r = 0.64, P = 0.003; r = 0.97, P < 0.0001). We found no significant correlation between SC and FC. In 27 samples from UC patients, the association of SC with FC and CRP were positive and significant (P = 0.004, estimate = 0.32; P = 0.0001, estimate = 0.002). The association between SC and symptom score was insignificant. In 49 samples from CD patients, the association between SC and CRP was significant (P = 0.02, estimate = 0.002) whereas associations between SC and FC and symptom score were insignificant. In the current pilot study, we found a correlation between SC and the endoscopically assessed inflammation in UC. SC may have the potential to improve disease monitoring of adolescent patients.