Endogenous estrogens affect multiple sensory systems, including those involved in processing noxious and painful stimuli. Extensive evidence demonstrates that estrogenic environmental pollutants have profound, negative effects on growth and reproductive physiology, but there is limited information about how estrogenic pollutants might affect sensory systems known to be modulated by endogenous estrogens. Here, we show that ethinyl estradiol, the most common artificial estrogen found in coastal marine environments, disrupts normal behavioral and neural responses to tissue injury in the sepiolid, Euprymna scolopes (Hawaiian bobtail squid), which inhabits shallow tropical waters close to dense human habitation. Behavioral hypersensitivity and neural plasticity that occur normally after tissue injury were impaired both under chronic estrogen exposure beginning during embryogenesis, or after a single, high dose co-incident with injury. This suggests that these naturally selected responses to injury, which function to protect animals from predation and infection risk, may be impaired by anthropogenic pollution.© 2020. Published by The Company of Biologists Ltd.