Abstract The duty of loyalty, or loyal cooperation, (Art. 4(3) TEE, ex Art. 10 EC) governs the interactions between the Union and national legal orders and is linked to fundamental principles, such as effectiveness, primacy and respect of the Member States’ autonomy. In the field of EU external relations, the duty of loyalty may express different facets of the Union interest. As an expression of the obligation to effectively implement common rules, the duty of loyalty permits to understand how a mixed agreement in its entirety has to be considered as a source of European Union law. Besides, the duty of loyalty implies the need to ensure the effectiveness of EU law obligations in the exercise of the Member States’ retained competence. It results from the recent case law of the Court of Justice that Member States have the obligation to eliminate not only established, but also hypothetical incompatibilities between common rules and their prior international commitments (Art. 351(2) TFEU, ex Art. 307(2)EC). Furthermore, the duty of loyalty implies an obligation for the Member States to facilitate the exercise of the Union competence. It is the basis of their obligation to refrain from adopting a unilateral position and, in some cases, to act in the interest of the Union. Finally, the duty of loyalty, through the duty of close cooperation, contributes to the fulfillment of the requirement of unity of the external representation of the European Union and its Member States.