Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and ω3 essential fatty acid levels and by an increased C20: 4ω6 C20: 5ω3 i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2; C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of ω6 and ω3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios ω6 ω3 and C20:4ω6 C20:5ω3 were calculated. Major depressed subjects had significantly higher C20:4ω6 C20:5ω3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased ω6 ω3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3ω3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total ω3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5ω3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.