Immune checkpoint inhibitors designed to reinvigorate immune responses suppressed by cancer cells have revolutionized cancer therapy. Similarities in immune dysregulation between cancer and infectious diseases have prompted investigations into the role of immune checkpoints in infectious diseases, including the therapeutic potential of immune checkpoint blockade and drug repurposing. While most research has centered around viral infections, data for bacterial infections are emerging. This systematic review reports on the in vivo effect of immune checkpoint blockade on bacterial burden and selected immune responses in preclinical studies of bacterial infection, aiming to assess if there could be a rationale for using immunotherapy for bacterial infections. Of the 42 analyzed studies, immune checkpoint blockade reduced the bacterial burden in 60% of studies, had no effect in 28% and increased the bacterial burden in 12%. Findings suggest that the effect of immune checkpoint blockade on bacterial burden is context-dependent and in part relates to the pathogen. Further preclinical research is required to understand how the therapeutic effect of immune checkpoint blockade is mediated in different bacterial infections, and if immune checkpoint blockade can be used as an adjuvant to conventional infection management strategies.