Analyzing 24-h urine for lithium after consumption of lithium-tagged foods or supplements provides a validated compliance marker but is laborious. Objective: Most studies involve blood sampling; therefore, we tested whether serum lithium concentration could be used as a compliance marker. Design: We used serum lithium as a compliance marker in a dietary trial and an evaluation study. Results: In the dietary trial, 78 volunteers consumed 500 mL yogurt tagged with lithium (250 μmol/d) for 6 wk. Serum lithium increased from 0.9 ± 0.3 to 6.6 ± 1.5 μmol/L, which was close to the predicted concentration, indicating that the subjects were highly compliant. However, the interindividual variability in serum lithium concentration was large. To test whether this variability resulted from compliance differences or natural variability, we performed an evaluation study: 12 subjects took a lithium supplement (250 μmol/d) for 13 d under supervision. Serum lithium increased from 0.14 ±0.03 to 3.9 ±0.8 μmol/L (range: 2.6-5.4 μmol/L); thus, there was wide interindividual variation in serum lithium despite 100␌ompliance. However, within-subject variability was small, with a CV of 7␏or serum lithium measured on 4 different days. We checked whether taking half the dose on each of 2 d (125 μmol lithium/d) would significantly lower serum lithium. Indeed, serum lithium dropped in all subjects, by a mean of 1.0 μmol/L on the first day (P < 0.0001) and by another 0.3 μmol/L on the second day (P = 0.0004). Thus, changes in serum lithium concentration of ≥1.0 μmol/L suggest altered compliance. Conclusion: Serum lithium concentrations after intake of lithum-tagged foods or supplements can be used to assess compliance in dietary trials.