Early life represents one of the highest incidence periods for early-life seizures (ELS). Patients with ELS are often refractory to anti-epileptic drugs. Here, I aimed to understand the effects of ELS on the immature brain to identify novel cellular targets using an ELS mouse model. I demonstrated for that ELS impaired the excitatory synaptic inputs into a specific subtype of interneurons, the FS interneurons. ELS significantly altered the probability of release and the readily releasable pools at the excitatory presynaptic terminals. This changed the short-term plasticity at these excitatory inputs and FS interneurons during repetitive excitatory activity. Additionally, ELS significantly depressed asynchronous neurotransmitter release at the excitatory inputs, resulting in impaired postsynaptic spike timing and temporal fidelity of the FS interneurons. These data demonstrated ELS-induced target specific modulations in FS interneurons and provided a novel cellular mechanism by which ELS alter the immature brain and disrupt the excitation/inhibition balance.