Acute injuries of the kidney or lung each represent serious, complex clinical problems, and their combination drastically decreases patient survival. However, detailed understanding of interactions between these two organs is scarce. To evaluate this further, we used the folic acid (FA) and myohemoglobinuria models of acute kidney injury (AKI) together with Pseudomonas aeruginosa inhalation to study kidney–lung cross-talk in mice during acute kidney and lung injury. Subgroups of mice received antineutrophil antibody or platelet-depleting serum to assess the role of neutrophil and platelets, respectively. AKI by itself did not cause clinically relevant acute lung injury. Pneumonia was neutrophil dependent, whereas pneumonia-induced AKI was platelet dependent. AKI attenuated pulmonary neutrophil recruitment and worsened pneumonia. Mice with AKI had lower oxygen saturations and greater bacterial load than mice without. Neutrophils isolated from mice with FA-induced AKI also had impaired transmigration and F-actin polymerization in vitro. Thus, during acute kidney and pneumonia-induced lung injury, clinically relevant kidney–lung interactions are both neutrophil and platelet dependent.