Abstract Selenium contributes to physiological functions through its incorporation into selenoproteins. It is involved in oxidative stress defense. A selenium deficiency results in the onset or aggravation of pathologies. Following a deficiency, the repletion of selenium leads to a selenoprotein expression hierarchy still misunderstood. Moreover, spirulina, a microalgae, exhibits antioxidant properties and can be enriched in selenium during its cultivation. Our objective was to determine the effects of a sodium selenite or selenium-enriched spirulina supplementation. Thirty-two female wistar rats were fed for 12 weeks with a selenium-deficient diet. After 8 weeks, rats were divided into 4 groups of 8 rats and were fed with water, sodium selenite (20µg Se/kg body weight), spirulina (3 g/kg bw) or selenium-enriched spirulina (20µg Se/kg bw + 3g spirulina/kg bw). In parallel, another group of 8 rats were fed with normal diet during 12 weeks. Selenium concentration and antioxidant enzyme activities (GPx, SOD, CAT) were measured in plasma, urines, liver, brain, kidney, heart and soleus. Expression of GPx (1, 3), Sel (P, S, T, W), SEPHS2, TrxR1, ApoER2 and Megalin were quantified in liver, kidney, brain and heart. Our results showed that a selenium deficiency leads to a growth retardation, reversed by selenium supplementation. All tissues displayed a decrease in selenium concentration following deficiency. Brain seemed protected. Our results demonstrated a hierarchy in selenium distribution and selenoprotein expression depending on selenium supplementation form. A supplementation of sodium selenite improved GPx activities and selenoprotein expression while a selenium-enriched spirulina was more effective to restore selenium concentration.