Objective: To test whether effects of multiple (up to 5) disasters on mental health responses were cumulative (additive effects), or whether an earlier disaster produced sensitization (higher) or habituation (lower) responses to a later one. Method: The Gulf Resilience on Women’s Health study interviewed 1,366 southern Louisiana women regarding their exposure to Hurricanes Katrina, Rita, Gustav, and Ike and the Gulf oil spill (measured several ways), and administered validated measures of symptoms of depression and posttraumatic stress disorder (PTSD). Multiple linear and logistic regression with disaster exposures entered singly, combined, and as an interaction were used to model mental health. Results: Both exposure to the oil spill and hurricane disaster were associated with likely depression and PTSD, consistent with a cumulative model, but we did not find statistical interactions that would suggest sensitization or habituation. When results were examined with continuous symptom measures of depression and PTSD, they were similar, with the exception that exposure to the oil spill and experiencing illness or injury because of the hurricane disaster showed a significant interaction (p < .05) in a manner consistent with a sensitization effect when predicting PTSD symptoms. The results of this study point mainly to a cumulative risk for the mental health effects of multiple disasters, although some indication of sensitization occurred among those with particularly severe experiences. There was no evidence for habituation. Conclusions: These findings may guide efforts to assist those in regions experiencing multiple disasters that occur in close sequence.