Cardinal Vincent Nichols and Bishop William Kenney, from the diocese of Birmingham, have released a statement calling the upsurge of violence a "tragedy" and saying the "violence should cease and that people whatever their differences should build a nation of peace."
The pair are also worried that violence could prevent South Sudan, which just celebrated five years of independence, from becoming a "successful" country.
The statement expresses condolences for families who have lost loved ones in the fighting as well as prayers from those who have fled the capital, Juba, searching for shelter, food and safety.
CAFOD, the international Catholic charity, is also mentioned and they ask that assistance is provided.
They say: "We ask that the international community takes this situation seriously and supports the efforts for peace which are being made by many agencies.
"We will ask CAFOD, already present in the country, as a matter of urgency, to determine what humanitarian action it can take.
"Our thoughts are with our brother Bishops in South Sudan and we assure them that they are not forgotten.
"We pray for peace and calm, and ask the Catholic Church in England and Wales to pray for the people of South Sudan.
"We ask the Lord to 'put an end to war' and to 'break the bow' and 'snap the spear'."
The bishops' words come after an increase in political tension and violence in Juba.
Conflict is mainly between forces loyal to President Salva Kiir Mayardit and those faithful to the vice-president James Wani Igga.
South Sudan became an independent country in 2011 and has a significant Christian population.
The international community is concerned that continued fighting might result in the country descending into another civil war just months after a ceasefire was agreed.