Abstract Background Measuring the presence and pattern of periportal fibrosis (PPF) in schistosomiasis mansoni (SM) is essential for diagnosing its clinical forms and detection of portal hypertension. For these evaluations, the gold-standard has been ultrasound scan (US) using Niamey classification, however it requires sophisticated equipment and well-trained operator. ELF (Enhanced Liver Fibrosis) is an index capable of quantifying liver fibrosis in chronic liver diseases, although there have been few studies evaluating PPF in SM. Aim To assess serum ELF levels according to the PPF patterns established by ultrasound using the Niamey classification in patients with schistosomiasis. Methods A cross-sectional, bidirectional analytical study was carried out with patients from an endemic area (patterns A, B, C and D) and from an SM reference outpatient clinic (patterns D, E and F). Clinical data and 10 mL of blood were collected, centrifuged and frozen to measure and calculate the score by the ELF™ Test (Atellica® IM), according to the equation: [ELF = 2.278 + 0.851 ln(HA) + 0.751 ln(PIIINP) + 0.394 ln(TIMP-1)] and expressed as a numerical value without unit. US using GE Healthcare Logic E (endemic area) or Siemens Acuson S2000 (outpatient clinic) equipment were performed by a single examiner. Results Of the 196 patients evaluated, 114 (58.2%) were women with a mean age of 45 ± 15.42 years. They had the following PPF patterns: 18 pattern A+B; 64 pattern C; 56 pattern D; 49 pattern E and 9 pattern F. The median ELF values were higher according to PPF progression in these 5 groups (p = 0.0021), respectively: (A+B = 8.36); (C = 8.40); (D = 8.64); (E = 8.99) and (F = 9.75). The ELF was able to differentiate patients without PPF, with mild, moderate and advanced PPF: A+B vs C vs D vs E+F (p = 0.0024), as well as patients with advanced PPF from those without fibrosis or with moderate fibrosis: A+B vs E+F (p = 0.0464) and C+D vs E+F (p = 0.0007). The index was also able to differentiate patients with absent or mild PPF from those with moderate or advanced PPF: A+B+C vs D+E+F (p = 0.0015). Conclusions The ELF showed great potential as a tool for assessing PPF in patients with schistosomiasis mansoni, being able to differentiate those with little fibrosis from those with moderate or advanced fibrosis.