Background: Patients with psoriasis may develop psoriatic arthritis (PsA), an inflammatory joint disorder. Measuring cellular communication network (CCN) expression levels can help in disease diagnosis and prognosis. The purpose of this study was to assess the diagnostic value of CCN1 and CCN3 expressions for PsA. Patients and methods: Thirty-seven PsA patients, 37 psoriasis patients, and 37 matched healthy controls participated in a case-control study. ELISA was used to detect protein levels while qRT-PCR was used to evaluate gene expression. Results: Patients with PsA and psoriasis had greater serum and expression levels of CCN1 compared to controls (p < 0.0001). Patients with PsA and psoriasis had greater serum and expression levels of CCN1 compared to controls (p= 0.003, p < 0.0001). Both CCN3 levels in PsA patients were greater than in controls (p < 0.0001), but patients with psoriasis did not significantly differ from controls (p=0.13, p=0.38). When compared to psoriasis patients, PsA patients had greater serum and expression levels of CCN3 (p < 0.0001). In terms of psoriasis duration and severity, CCN1 exhibited a positive relation. It was shown that CCN3 and both the duration and severity of arthritis correlated positively. All markers were positively correlated with inflammatory markers. Conclusions: The most accurate marker for PsA detection was CCN3 expression, followed by the serum level of CCN1. However, CCN1 expression was the most accurate marker for the differentiation between psoriasis and PsA, followed by CCN3 expression. CCN3 could be a marker for PsA severity. These preliminary data need further studies to confirm their findings.