We investigated the association of sickle cell anemia (SCA) vaso-occlusive crisis (VOC) with depression, anxiety, and stress disorders among Bahraini patients and controls. This was a cross-sectional study that involved administering Depression Anxiety Stress Scales (DASS-21) consisting of structured depression, anxiety, and stress scales to SCA patients with (n=138) and without (n=105) VOC. Multinomial regression and correlation analysis were used in assessing the association of VOC with depression and/or anxiety and/or stress, after adjusting for other covariates. Significantly higher proportion of VOC patients was found among the severe-extremely severe anxiety (P<0.002) and stress (P=0.001) groups; the frequency of depressed patients was comparable between the 2 groups. Adjusting for age, sex, income, number of affected individuals per family, and HbS levels, mild-moderate (P=0.042; odds ratio=2.00; 95% confidence interval=1.03-3.91) and severe-extremely severe (P=0.004; odds ratio=4.43; 95% confidence interval=1.59-12.34) anxiety were independently associated with VOC. Both depression and stress were not associated with VOC after adjusting for these covariates. These results suggest a positive contribution of VOC to the increased rates of anxiety disorders among SCA patients, thereby recommending counseling SCA patients with repeated VOC for these psychologic comorbidities, in particular anxiety.