Aim: It is proven that pretreatment lymphopenia is a biomarker for poor prognosis at late stage solid malignancies. The purpose of the present study is to investigate the effects of pretreatment lymphopenia on prognosis and hematological toxicity in patients treated with first step systemic chemotherapy. Material and Method: Lymphocytes were counted for 386 patients with colorectal cancer before treatment. Overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were calculated. Results: Three hundred and eighty-six patients were included in the study. The mean age was 57.4. One hundred and sixty patients were women (41%), 226 were men (59%). Mean pretreatment lymphopenia was 1964/microliter. There was no relation between lymphopenia and age, gender, performance status, the presence of metastasis at the time of diagnosis, the purpose of chemotherapy either being adjuvant or metastatic and progression into hematological toxicity (p >0.05). One-, two- and five-year overall survival was significantly lower in patients with lymphopenia when considering all patients (p:0.033). Lymphopenia was present in 27 patients (7%) who had metastasis at the time of diagnosis and 13 of them deceased in the follow-up. One-, two- and five-year overall survival was significantly lower in those patients with metastasis who have lymphopenia (p <0.043). Discussion: The present study supports that pretreatment lymphocyte count in colorectal cancer can be a simple yet useful prognostic and predictive marker. Overall survival found to be significantly lower in patients with low pretreatment lymphocyte counts (p <0.05). To the best of our knowledge, the present study has the largest patient population in the literature which investigates the relationship between colorectal cancer and lymphopenia.