While antibiotics are clearly important treatments for infection, antibiotic-induced modulation of the immune system can have detrimental effects on pathogen clearance and immune functionality, increasing the risk of secondary infection. These injurious consequences may be mediated, at least in part, through effects on the mitochondria, the functioning of which is already compromised by the underlying septic process. Here, we review the complex interactions between antibiotic administration, immune cell and mitochondrial dysfunction.