Background This cohort study assessed urinary eosinophil cationic protein (ECP) as an indicator for urinary tract morbidity and inflammation indication related to single-dose or dual-dose praziquantel (PZQ) treatment. Methods Urinary ECP was measured at baseline, 24 h and 9 weeks after treatment (baseline 305, follow-up 204 participants, ages 2–40 years). Results ECP was significantly associated with the intensity of infection at baseline (p<0.05). Levels at baseline were 8.31 times higher (p<0.01) in participants with bladder morbidity than in those without. There was no correlation with kidney morbidity and no significant effect of a repeated dose of PZQ 40 mg/kg. Baseline ECP and ECP after 9 weeks were associated with microhaematuria (geometric mean ratio at baseline 7.56 [95% confidence limit {CL} 2.34–24.45]; p<0.01) and macrohaematuria (geometric mean ratio at baseline 6.22 [95% CL 2.71–14.24]; p<0.001). Mean levels of ECP dropped significantly during the first follow-up period and far less so in the second follow-up period (mean ECP at baseline: 70.8 ng/mL; ECP at 24 h: 24.5 ng/mL; ECP at 9 weeks: 14.6 ng/mL). Conclusion The urine ECP decrease happened immediately after treatment, reflecting the rapid action of PZQ on eggs in the bladder tissue. ECP in urine can be used as an indirect marker of the degree of local inflammatory reaction in the bladder and is not significantly affected by a repeated dose of PZQ.