We prospectively estimated the CRP and erythrocyte sedimentation rate (ESR) level in the blood of patients with systemic lupus erythematosus (SLE), with aim to find the difference between relapse and infection, especially because the high fever is the same clinical sign for both. After following this problem, considering the relation between SLE and infection, we have found that: When SLE is active disease, the infection is common complication, Immunosuppressive therapy, particularly with steroids, prepares the conditions for infection, Infection and SLE are going together, and here is believe that infection is making the worsening of basic disease, A lot of SLE syndromes are differentiated with difficulties from syndromes caused from infection (pneumonia, arthritis, serositis). During 2 (two) years follow up of 10 patients suffering from SLE and fulfilled ARA criteria, we found 5 relapses and 3 infections, and all of them were followed and analyzed. We used the additional criteria for the estimation of the disease activity every patient separately. The CRP blood level was measured every month. According to a lot of clinicians, normal values of CRP are 0-0.5 mg/dl (0-5 mg/L) and ESR between 12-20 mm. Levels over 15 mg/L (1.5 mg/dl) are found with 4 SLE patients (5 SLE relapses), and 2 patients with infections (3 cases of infection). The median value of CRP in the course of infection was more than 60 mg/L, in comparison with SLE relapse (16.5 mg/L). All patients with SLE relapse had increased ESR level, but CRP wasn't, while with infection ESR and CRP were regularly increased in all cases. Measuring CRP in SLE is helpful in differentiating between infection and relapse, only under one condition: that serositis previously wasn't present.