Background: Appendicitis is one of the most common surgical emergencies globally and it can both be difficult to diagnose but also to differentiate complicated from uncomplicated appendicitis preoperatively. The objective of this scoping review was to develop an overview of biomarkers in blood discriminating complicated from uncomplicated appendicitis and characterize their applicability in an acute setting including time, cost, and analysis technique required as well as their individual precision. Method: This scoping review was reported in accordance with PRISMA-ScR. The included studies had to report on biomarkers measured in the blood for at least ten patients with suspected appendicitis. A systematic literature search was conducted on August 28, 2022, in PubMed and Embase but restricted to articles published in January 2000 and onwards. A protocol was uploaded to Open Science Framework prior to data extraction. Results: A total of 65 biomarkers were included from 52 studies, covering 14,312 patients. There was 60% routine- and 40% novel biomarkers based on the reported analysis technique. The most frequently investigated biomarkers within each group were white blood cell count and procalcitonin. The routine biomarkers were of low financial cost but poor diagnostic accuracy with sensitivity ranging between 15 and 100% and specificity between 27 and 100%. Novel markers were costly ranging from 275 to 800$, and their diagnostic accuracy was based on limited population sizes (median 34 patients) and reported for only 5% of the novel markers. Conclusion: Routine biomarkers were applicable in an acute setting but had poor diagnostic accuracy. Novel biomarkers are being investigated for potential, but the concept is still premature due to lack of diagnostic accuracy studies reporting cost-benefit for individual markers and whether they can be applied in an acute setting.