We examined the influence of the reproductive cycle and environmental factors on variations of the condition index (CI), tissue dry mass, shell size, total lipid content, and relative percent of fatty acids in the mussel, Perna perna. Spat or juveniles were reared to commercial size (70 mm) in suspension culture in the Golfo de Cariaco, Venezuela between May and October 2004. The dry mass of soft tissues and shell, a visual assessment of gonadal status and the organism lipid profile were established every fortnight. In parallel, we measured the environmental conditions, following chlorophyll a, salinity, temperature and seston levels. After an initial decrease, the CI rose and remained high until August after which it decreased continuously until October. Total lipid values also decreased initially, after which they showed two periods of rapid recuperation and depletion, the first between May and August and the second between August and October. Similar tendencies were noted in the fatty acids, C18:3n-3, C18:4n-3 and C22:6n-3. Correlation analysis found no significant relationships between environmental parameters and the variations in total lipids. However, significant correlations were noted between fatty acids and specific environmental parameters. In particular, temperature was inversely correlated with C14:0, C16:1n-7, C18:0, C18:1n-9 and 20:5n-3. Chlorophyll a was positively correlated with C14:0, C16:1n-7, C18:1n-7, C18:4n-3 and 20:4n-6. On the other hand, gametogenesis had an effect on C14:0, C16:1n-7, C18:1n-9 and C18:1n-7, while spawned and gonadal regression states had an effect on fatty acid 20:4n-6. Temperature and chlorophyll a levels strongly influenced the proportion of mussels spawning, suggesting that their influence upon lipid composition may be secondary to their impact upon reproduction. Despite the thermal stability of this tropical system, the lipid composition of mussels changed markedly during the study, reflecting the central role of diet and reproductive investment upon lipid composition.