Premature infants with placental infection and adult stroke patients with fever have worse outcomes following intracerebral hemorrhage (ICH). We hypothesized that immune pre-activation would aggravate brain injury in mouse brain following ICH. The immune system of 2-day, 10-day and 7-week young adult CD1 mice was stimulated by intraperitoneal injection of concanavalin A (ConA), lipopolysaccharide (LPS) or polyinosinic-polycytidilic acid (PolyI:C) 12 h prior to intracerebral injection of blood. Two days later, brain damage and inflammation were worse in 2-day mice that had received LPS. The other agents had less consistent effects in 2-day mice. Brain damage in young adults was aggravated less after immune stimulation. These data suggest that immune pre-activation modifies hemorrhagic brain injury in immature mouse brain.