Objectives This study aimed to evaluate the eicosanoid and pro-resolutive parameters in Post Covid Syndrome (PCS) patients during 12 weeks of a supplementation with a marine oil enriched in SPMs. Patient and methods The study was conducted in 53 adult patients with a PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: Polyunsaturated fatty acids: EPA, DHA, ARA, DPA, Specialized Pro-resolving mediators (SPMs) 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different amounts of intake were evaluated: daily use of 500mg, 1500mg, and 3000mg were compared to a control group without use of the product. Results In the serum from PCS patients, an increase of 17-HDHA, 18-HEPE, 14-HDHA could be observed. Also, a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected. Both differences were significant (p < 0.05). There were no differences between the three treatment groups. Fatigue and dyspnoea showed a trend to improve after supplementation in all groups. Conclusions A clear enrichment in serum of the three monohydroxylated SPMs could be observed also at a dosage of 500 mg per day. In the same way, a clear improvement in fatigue and dyspnoea was observed with this dosage. Clinical Trial Registry: ISRCTN13270662.