Winter flounder from New Haven, Connecticut were evaluated for fin rot disease. Blood samples collected from healthy and diseased fish were used to measure bilirubin, calcium, hematocrit, inorganic phosphorus, osmolality, and total protein. Blood measurements were significantly affected by the presence of fin rot disease and by sampling mode (bled immediately or after 18 h). A reduction in blood chemistry values was associated with fin rot disease. Logistic regression modeling was used to identify explanatory variables contributing to the fin rot outcome in winter flounder. Blood constituent levels were higher in fish bled immediately versus 18 h post-capture, especially among fish without fin rot, suggesting that a waiting period is necessary for blood values to stabilize following initial sampling stress. This study presents evidence that winter flounder blood chemistry and hematocrit measurements are affected by fin rot disease.