Purpose To find if there is any potential benefit of serum Sphingosine-1-Phosphate (S1P) level in the diagnosis of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC). Methods and materials Patients newly or previously diagnosed with BPS/IC between September 2017 and December 2018 were included. Healthy individuals who volunteered to enter the study were included as control group. The measurements of serum S1P in both groups were compared. Multiple regression analysis was conducted to find out the significant factors affecting S1P results. Results A total of 47 BPS/IC patients and 47 healthy controls were included. BPS/IC patients were older than controls (48.5 +/- 12.4 vs 38.9 +/- 8.1 years, p < 0.001). The female-to-male ratio was 46/1 for patient group and 29/18 for controls. 68.1% (32/47) of BPS/IC patients had previous treatments. 55.3%(26/47) of patient group had accompanying medical or psychiatric disease. The mean serum S1P level was notably elevated in BPS/IC group (median 213.6, mean +/- SD 258.9 +/- 167.2 vs median 125.4, mean +/- SD 142.9 +/- 54.8; p < 0.001). Using ROC curve analysis, a value of 165 was a good cutoff point between patient and control groups (AUC = 0.761, p < 0.001). On multiple regression analysis, being BPS/IC patient was the only significant predictor of a serum S1P level above the cutoff point documented on ROC analysis (OR 5.9; 95% CI 1.8-19.9; p = 0.004). Conclusion Sphingosine-1-phosphate (S1P) pathway seems to have a potential role in the pathogenesis of BPS/IC. High serum S1P level might support the diagnosis of BPS/IC.