Postecdysial mineralization in crustaceans involves the deposition of carbonate salts, such as calcium carbonate, to the organic matrix. Because of the resemblance between Pb2+ and Ca2+, the present study was carried out to investigate whether Pb is incorporated into the new shell during postecdysial mineralization using the blue crab (Callinectes sapidus) as the model crustacean. It was hypothesized that injected Pb would be deposited in the shell via calcium transporters in the epidermis during the mineralization process. Postecdysial blue crabs were injected with two doses of 5 µg Pb/g wet weight each in lead acetate, and then Pb, Ca, and Mg contents were analyzed in the exoskeleton, while only Pb bioaccumulation was quantified for the hepatopancreas, gills, muscles, and hemolymph. The results showed a statistically nonsignificant increase in exoskeletal Pb content in Pb‐treated crabs compared to control, suggesting that exoskeletal Pb may not be a sensitive proxy for aquatic Pb pollution. There was a significant decrease in Ca content in Pb‐treated crabs, suggesting that Pb hindered the deposition of Ca to crab exoskeleton, thereby obstructing calcification. A trend of a decrease in exoskeletal Mg was also observed in Pb‐treated crabs. There was a significant increase in Pb content found in the gills, hepatopancreas, muscle, and hemolymph in Pb‐treated crabs. The rank of the Pb level among three soft tissues in a decreasing order is hepatopancreas > gill > muscle. This is the first study to present evidence that Pb disrupts postecdysial exoskeletal calcification in a crustacean. Environ Toxicol Chem 2022;41:474–482. © 2021 SETAC