Most people on folic acid to boost erythropoiesis and prophylactic antimicrobials, the standard management of steady state sickle cell disease (SCD), have unacceptable numbers of crises. The objective of this study was to evaluate the effects of adding multimodal therapy with potassium thiocyanate and omega-3 fatty acids to the standard management of steady state SCD. Pre- and post-treatment numbers of crises and other disease indices were compared in 16 HbSS individuals on folic acid and paludrine after 12 months of adding eicosapentaenoic acid 15 mg/kg/day, docosahexaenoic acid 10 mg/kg/day, and potassium thiocyanate 1-2 mL/day, each milliliter of which contained 250 mg of thiocyanate and 100 micrograms of iodine to prevent hypothyroidism: a possible side-effect due to competitive inhibition of the transport of iodide into the thyroid gland by thiocyanate. Median number of crises reduced from 3/yr to 1/yr (P < 0.0001). There was no evidence of impaired thyroid function. Plasma level of tri-iodothyronine improved (P < 0.0001). Steady state full blood count and bilirubin level did not change significantly. The findings suggest that addition of potassium thiocyanate and eicosapentaenoic and docosahexaenoic acids to standard management of steady state SCD reduces the number of crises. This observation needs to be evaluated in larger studies.