Background: Continuous monitoring of hemoglobin (HB) and hematocrit (HCT) during hemodialysis could improve fluid management and patient safety. The Fresenius 5008 dialysis machine includes an ultrasound-based sensor that estimates HB and HCT values, though its accuracy compared to standard laboratory measurements remains unclear. Methods: This exploratory observational study assessed the agreement between sensor-derived and laboratory-derived HB and HCT values in 20 patients at the start of hemodiafiltration. A total of 177 paired blood samples were collected. Results: Sensor values significantly underestimated laboratory HB (9.61 vs. 11.31 g/dL) and HCT (27% vs. 34%) (p < 8 × 10⁻²⁵). Correlations were strong for both parameters (HB: r = 0.788; HCT: r = 0.876). Regression analyses revealed consistent proportional bias. Applying a fixed correction of +1.69 g/dL for HB and +7.55% for HCT eliminated the statistical differences and reduced intercepts in regression models. Bland–Altman plots confirmed improved agreement post-correction. Albumin levels correlated modestly with error magnitude. Conclusions: HB and HCT values from the Fresenius 5008 sensor are strongly correlated with laboratory data but are systematically underestimated at treatment start, likely due to hemodilution. Applying fixed correction factors improves accuracy and supports the sensor’s use for real-time monitoring.