Collecting blood spots from newborns is a common procedure used to diagnose multiple health conditions. Fingerstick blood samples are routinely collected from children to diagnose elevated blood lead levels. In our study, we wanted to test the feasibility of using a high-power energy-dispersive X-ray fluorescence (EDXRF) device to accurately measure the concentration of lead in blood spots. We created spotted standards of a known concentration of lead on a filter paper at different volumes and concentrations. We determined the detection limit for lead through repeated measurements of our standards and calibration line slopes. We also tested the variability of the measured lead concentration across procedures and spotted blood volumes and found no significant additions to uncertainty in measurements. Finally, we compared blood lead concentrations measured by EDXRF and atomic absorption spectroscopy (AAS) and found EDXRF to be a significant predictor of blood lead (n = 22, R = 0.98, p value <0.001) with an average detection limit of 1.7 μg/dL of blood lead. This detection limit is similar to that of the AAS technique, which is commonly used in clinical testing laboratories for blood lead surveillance. These findings provide a proof of concept that blood spots measured by EDXRF may be used as a surveillance tool for lead exposure, even at elevated blood lead levels of 2-3 μg/dL.