In this paper, we reported in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)2(LN)x(H2O)(2-x)]·yH2O; x=1-2, HLaw = 2-hydroxy-1,4-naphthoquinone, and LN = heterocyclic N-donor ligand. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB) both by lipopolysaccharide (LPS) and TNF-alpha at 100 nM level in the similar manner as the reference drug prednisone (at 1 µM level) and were also able to suppress the inflammatory response in vivo in hind-paw edema model on rats. The most active complexes 1–3 diminished the formation of edema similarly as the reference drug indomethacine. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found in vitro. The overall effect of the complexes, dominantly 1–3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects.