The aim of this study was to explore a potential link between psychosocial stress and cocaine dependence among 36 non-treatment-seeking individuals enrolled in a brain imaging protocol. Stress was assessed using computerized multidimensional instruments, including the Profile of Mood States (POMS) and Speilberger State-Trait Anxiety Inventory (STAI). Additional clinical assessments employed were the Addiction Severity Index and the Hamilton Rating Scale for Depression (HRSD). Based on the median POMS' tension-anxiety scale score the entire sample was divided into two groups, those with high and low levels of stress. The two groups (n = 16 and 20) were similar in terms of age, gender distribution, and severity of addiction. Compared with the low stress group, high-stress individuals displayed significantly longer duration of cocaine use, greater POMS, STAI-state, STAI-Trait, and HRSD scores. Our results replicate those of prior reports implicating stress in the course of cocaine dependence and extend these prior findings by 1) including a new subject population of non-treatment-seekers and 2) by suggesting that the stress-cocaine link may be generalizable to psychosocial stress and negative affective states defined by POMS, STAI, and HRSD scores.